Exploring the optimal lower blood pressure boundary during endovascular thrombectomy in patients with large vessel occlusion.

BACKGROUND: Current guidelines advocate for maintaining BP level below 180/105 mmHg during EVT, determining the safe lower boundary remains primarily consensus-driven by experts. This study aims to delve into the correlation between various targets of lower boundary for systolic and diastolic BP (SBP and DBP) during EVT and 3-month functional outcomes. METHODS: A cohort study was conducted across two EVT-capable centers, enrolling patients with large artery occlusion undergoing EVT within 8 h of stroke onset. Mean BP values during EVT were meticulously recorded, and logistic regression models were utilized to evaluate the correlation between outcomes and diverse lower boundary targets for SBP and DBP. Additionally, logistic regression models investigated the relationship between periprocedural BP variability and subsequent outcomes. RESULTS: Among the 201 patients included, having a SBP higher than 130 or 140 mmHg showed an independent association with increased good functional outcomes at 3 months (adjusted odds ratio, aOR 2.80, 95% Cis, 1.26-6.39 for 140 mmHg; aOR 2.34, 95% Cis, 1.03-5.56 for 130 mmHg). Additionally, an SBP exceeding 130 mmHg was correlated with decreased 3-month mortality (aOR, 0.24, 95% CI 0.07-0.74). No significant relationship was observed between DBP and functional outcomes. Patients with higher periprocedural SBP coefficient variance exhibited a decreased rate of good functional outcomes at 3 months (aOR, 0.42, 95% CI, 0.18-0.96). CONCLUSIONS: A SBP range above 130-140 mmHg could potentially serve as a safe lower boundary during EVT, while minimizing BP fluctuations may correlate with improved post-EVT functional outcomes.

Enhancing the trustworthiness of chaos and synchronization of chaotic satellite model: a practice of discrete fractional-order approaches.

Accurate development of satellite maneuvers necessitates a broad orbital dynamical system and efficient nonlinear control techniques. For achieving the intended formation, a framework of a discrete fractional difference satellite model is constructed by the use of commensurate and non-commensurate orders for the control and synchronization of fractional-order chaotic satellite system. The efficacy of the suggested framework is evaluated employing a numerical simulation of the concerning dynamic systems of motion while taking into account multiple considerations such as Lyapunov exponent research, phase images and bifurcation schematics. With the aid of discrete nabla operators, we monitor the qualitative behavioural patterns of satellite systems in order to provide justification for the structure's chaos. We acquire the fixed points of the proposed trajectory. At each fixed point, we calculate the eigenvalue of the satellite system's Jacobian matrix and check for zones of instability. The outcomes exhibit a wide range of multifaceted behaviours resulting from the interaction with various fractional-orders in the offered system. Additionally, the sample entropy evaluation is employed in the research to determine complexities and endorse the existence of chaos. To maintain stability and synchronize the system, nonlinear controllers are additionally provided. The study highlights the technique's vulnerability to fractional-order factors, resulting in exclusive, changing trends and equilibrium frameworks. Because of its diverse and convoluted behaviour, the satellite chaotic model is an intriguing and crucial subject for research.

Novel inflammatory and insulin resistance indices provide a clue in cerebral amyloid angiopathy.

This study investigated the correlation of newly identified inflammatory and insulin resistance indices with cerebral amyloid angiopathy (CAA), and explored their potential to differentiate CAA from hypertensive arteriopathy (HA). We retrospectively analyzed 514 consecutive patients with cerebral small vessel disease (CSVD)-related haemorrhage, comparing the differences in novel inflammatory and insulin resistance indices between patients with CAA and HA. Univariate regression, LASSO and multivariate regression were used to screen variables and construct a classification diagnosis nomogram. Additionally, these biomarkers were explored in patients with mixed haemorrhagic CSVD. Inflammatory indices were higher in CAA patients, whereas insulin resistance indices were higher in HA patients. Further analysis identified neutrophil-to-lymphocyte ratio (NLR, OR 1.17, 95% CI 1.07-1.30, P < 0.001), and triglyceride-glucose index (TyG, OR = 0.56, 95% CI 0.36-0.83, P = 0.005) as independent factors for CAA. Therefore, we constructed a CAA prediction nomogram without haemorrhagic imaging markers. The nomogram yielded an area under the curve (AUC) of 0.811 (95% CI 0.764-0.865) in the training set and 0.830 (95% CI 0.718-0.887) in the test set, indicating an ability to identify high-risk CAA patients. These results show that CSVD patients can be phenotyped using novel inflammatory and insulin resistance indices, potentially allowing identification of high-risk CAA patients without haemorrhagic imaging markers.

Evaluating the utility of ZNF331 promoter methylation as a prognostic and predictive marker in stage III colon cancer: results from CALGB 89803 (Alliance).

While epigenomic alterations are common in colorectal cancers (CRC), few epigenomic biomarkers that risk-stratify patients have been identified. We thus sought to determine the potential of ZNF331 promoter hypermethylation (mZNF331) as a prognostic and predictive marker in colon cancer. We examined the association of mZNF331 with clinicopathologic features, relapse, survival, and treatment efficacy in patients with stage III colon cancer treated within a randomized adjuvant chemotherapy trial (CALGB/Alliance89803). Residual tumour tissue was available for genomic DNA extraction and methylation analysis for 385 patients. ZNF331 promoter methylation status was determined by bisulphite conversion and fluorescence-based real-time polymerase chain reaction. Kaplan-Meier estimator and Cox proportional hazard models were used to assess the prognostic and predictive role of mZNF331 in this well-annotated dataset, adjusting for clinicopathologic features and standard molecular markers. mZNF331 was observed in 267/385 (69.4%) evaluable cases. Histopathologic features were largely similar between patients with mZNF331 compared to unmethylated ZNF331 (unmZNFF31). There was no significant difference in disease-free or overall survival between patients with mZNF331 versus unmZNF331 colon cancers, even when adjusting for clinicopathologic features and molecular marker status. Similarly, there was no difference in disease-free or overall survival across treatment arms when stratified by ZNF331 methylation status. While ZNF331 promoter hypermethylation is frequently observed in CRC, our current study of a small subset of patients with stage III colon cancer suggests limited applicability as a prognostic marker. Larger studies may provide more insight and clarity into the applicability of mZNF331 as a prognostic and predictive marker.

Piperidine and Pyridine Series Lead-Free Dion-Jacobson Phase Tin Perovskite Single Crystals and Their Applications for Field-Effect Transistors.

Two-dimensional (2D) organic-inorganic metal halide perovskites have gained immense attention as alternatives to three-dimensional (3D) perovskites in recent years. The hydrophobic spacers in the layered structure of 2D perovskites make them more moisture-resistant than 3D perovskites. Moreover, they exhibit unique anisotropic electrical transport properties due to a structural confinement effect. In this study, four lead-free Dion-Jacobson (DJ) Sn-based phase perovskite single crystals, 3AMPSnI4, 4AMPSnI4, 3AMPYSnI4, and 4AMPYSnI4 [AMP = (aminomethyl)-piperidinium, AMPY = (aminomethyl)pyridinium] are reported. Results reveal structural differences between them impacting the resulting optical properties. Namely, higher octahedron distortion results in a higher absorption edge. Density functional theory (DFT) is also performed to determine the trends in energy band diagrams, exciton binding energies, and formation energies due to structural differences among the four single crystals. Finally, a field-effect transistor (FET) based on 4AMPSnI4 is demonstrated with a respectable hole mobility of 0.57 cm2 V-1 s-1 requiring a low threshold voltage of only -2.5 V at a drain voltage of -40 V. To the best of our knowledge, this is the third DJ-phase perovskite FET reported to date.

Dosimetric Correlation of Acute Radiation Dermatitis in Patients With Breast Cancer Undergoing Hypofractionated Proton Beam Therapy Using Pencil Beam Scanning.

PURPOSE: Pencil-beam scanning (PBS) is a modern delivery technique used in proton beam therapy (PBT) to reduce normal tissue reactions. No dosimetric correlation between dermatitis and PBS has been reported for breast cancer. The current study aimed to investigate the factors associated with grade 2 or higher dermatitis in patients with breast cancer undergoing PBT using PBS. METHODS: The medical data of 42 patients with breast cancer who underwent adjuvant radiotherapy between December 2019 and September 2023 were reviewed. All patients received hypofractionated radiotherapy (HFRT), either 26 Gy (relative biological effectiveness [RBE])/five fractions or 40.05 or 43.5 Gy (RBE)/15 fractions, for the whole breast/chest wall with or without nodal irradiation. The duration of acute radiation dermatitis was defined as within 90 days from the start of radiotherapy. The Kaplan-Meier method and Cox proportional hazards model were used for univariate and multivariate analyses of the actuarial rates of grade 2-3 dermatitis. RESULTS: Twenty-two (52.4%) and 20 (47.6%) patients were diagnosed with grade 1 and 2 dermatitis, respectively. Multivariate analysis revealed a clinical target volume (CTV) ≥ of 320 cc (p = 0.035) and a skin dose of D10cc ≥ 38.3 Gy (RBE) (p = 0.009) as independent factors of grade 2 dermatitis. The 10-week cumulative grade 2 dermatitis rates were 88.2%, 39.4%, and 8.3% (p < 0.001) for patients with both high, either high, and neither high CTV and D10cc, respectively. CONCLUSION: To the best of our knowledge, this is the first study on dosimetric correlations for dermatitis in patients with breast cancer who underwent hypofractionated PBT using PBS. In the era of HFRT, skin dose modulation using PBS may reduce the incidence of dermatitis.

The risk of free flap revision and subsequent medical costs in patients with hypopharyngeal cancer.

BACKGROUND: Few studies have examined the preoperative risks and healthcare costs related to free flap revision in hypopharyngeal cancer (HPC) patients. METHODS: A 20-year retrospective case-control study was conducted using the Chang Gung Research Database, focusing on HPC patients who underwent tumor excision and free flap reconstruction from January 1, 2001, to December 31, 2019. The impacts of clinical variables on the need for re-exploration due to free flap complications were assessed using logistic regression. The direct and indirect effects of these complications on medical costs were evaluated by causal mediation analysis. RESULTS: Among 348 patients studied, 43 (12.4%) developed complications requiring re-exploration. Lower preoperative albumin levels significantly increased the risk of complications (OR 2.45, 95% CI 1.12-5.35), especially in older and previously irradiated patients. Causal mediation analysis revealed that these complications explained 11.4% of the effect on increased hospitalization costs, after controlling for confounders. CONCLUSIONS: Lower preoperative albumin levels in HPC patients are associated with a higher risk of microvascular free flap complications and elevated healthcare costs, underscoring the need for enhanced nutritional support before surgery in this population.

CCT6A facilitates lung adenocarcinoma progression and glycolysis via STAT1/HK2 axis.

BACKGROUND: Chaperonin Containing TCP1 Subunit 6 A (CCT6A) is a prominent protein involved in the folding and stabilization of newly synthesized proteins. However, its roles and underlying mechanisms in lung adenocarcinoma (LUAD), one of the most aggressive cancers, remain elusive. METHODS: Our study utilized in vitro cell phenotype experiments to assess CCT6A's impact on the proliferation and invasion capabilities of LUAD cell lines. To delve into CCT6A's intrinsic mechanisms affecting glycolysis and proliferation in lung adenocarcinoma, we employed transcriptomic sequencing and liquid chromatography-mass spectrometry analysis. Co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (CHIP) assays were also conducted to substantiate the mechanism. RESULTS: CCT6A was found to be significantly overexpressed in LUAD and associated with a poorer prognosis. The silencing of CCT6A inhibited the proliferation and migration of LUAD cells and elevated apoptosis rates. Mechanistically, CCT6A interacted with STAT1 protein, forming a complex that enhances the stability of STAT1 by protecting it from ubiquitin-mediated degradation. This, in turn, facilitated the transcription of hexokinase 2 (HK2), a critical enzyme in aerobic glycolysis, thereby stimulating LUAD's aerobic glycolysis and progression. CONCLUSION: Our findings reveal that the CCT6A/STAT1/HK2 axis orchestrated a reprogramming of glucose metabolism and thus promoted LUAD progression. These insights position CCT6A as a promising candidate for therapeutic intervention in LUAD treatment.

Mitigating treatment failure of pulmonary pre-extensively drug-resistant tuberculosis: The role of new and repurposed drugs.

BACKGROUND: Pre-extensively drug-resistant tuberculosis (pre-XDR-TB), defined as multidrug-resistant TB (MDR-TB) with additional resistance to any fluoroquinolone (FQ) is difficult to treat. We assessed whether the use of new or repurposed drugs (bedaquiline, delamanid, linezolid, carbapenem, clofazimine, pretomanid) mitigated treatment failure of pre-XDR-TB. METHODS: MDR-TB patients managed in the Taiwan MDR-TB consortium between July 2009-December 2019 were eligible. Treatment outcomes at 30 months were assessed. Logistic regression models were constructed to investigate factors associated with treatment outcomes. RESULTS: 109 patients with FQ-resistant MDR-TB and 218 patients with FQ-susceptible MDR-TB were included. 60 (55.1%) patients with FQ-resistant MDR-TB and 63 (28.9%) patients with FQ-susceptible MDR-TB have been treated with new or repurposed drugs (p < 0.01). Of the 218 patients with FQ-susceptible MDR-TB, 187 (85.8%) had treatment success, 30 (13.8%) died, no treatment failure, and 1 (0.5%) was loss-to-follow-up; of the 109 patients with FQ-resistant MDR-TB, 78 (71.6%) had treatment success, 21 (19.3%) died, 9 (8.3%) had treatment failure, and 1 (0.9%) was loss-to-follow-up (p < 0.01). The use of new or repurposed drugs was not associated with treatment outcomes among patients with FQ-susceptible MDR-TB. No patients with FQ-resistant MDR-TB treated with ≥2 new or repurposed drugs within 6 months of treatment initiation had treatment failure (p = 0.03). Patients with FQ-resistant MDR-TB treated with 1 new or repurposed drugs was more likely to have treatment failure as compared with patients not treated with new or repurposed drugs (adjOR 7.06, 95% CI 1.72-29.06). CONCLUSIONS: Proper use of new or repurposed anti-TB drugs can mitigate treatment failure in FQ-resistant MDR-TB.

The novel HLA-DPB1*05:01:20 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DPB1*05:01:20 differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 3.

Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days.

BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

Pelvic hematoma: The same complication with different etiology after patent foramen ovale closure.

Well-known complication associated with patent foramen ovale (PFO) closure include infection, acute cardiac tamponade, and local complications such as adjacent arterial or nerve damage, hemorrhage, and thrombophlebitis. Pelvic hematoma is rare and potentially fatal complication. This paper reports two cases of severe hemorrhagic shock within1 day after PFO closure. Both female patients presented to our department with history of headaches and were diagnosed with PFO. Both patients underwent percutaneous PFO closure from the right femoral vein. One day after the procedure, both patients experienced pelvic hematoma and were successfully rescued by compression hemostasis and uterine artery embolization. Both patients recovered well during follow-up. Life-threatening pelvic hematoma associated with PFO closure has a certain incidence and should be considered. Peripheral vascular complications after PFO closure can be safely treated but should not be ignored. We believe that the prevention of vascular mechanical damage during surgery is important. The possibility of spontaneous uterine artery rupture should be considered for unexplained pelvic hematoma. Although it is a rare complication, severe bleeding after PFO closure remains unpredictable. Timely and correct diagnosis and appropriate treatment are required. If the timing is delayed, there could be serious consequences.

Nonlinear Relationship Between Homocysteine and Mild Cognitive Impairment in Early Parkinson's Disease: A Cross-Sectional Study.

Background: Cognitive impairment, a prevalent non-motor symptom in advanced Parkinson's disease (PD), has been associated with hyperhomocysteinemia, an important risk factor for PD progression and cognitive decline in PD. However, evidence regarding the association between homocysteine (Hcy) and cognitive function during early PD remains insufficient. Therefore, this study aims to examine the correlation between Hcy levels and cognitive function in the early stage of PD. Methods: The study included 218 individuals in the early stages of PD who were consecutively admitted to the Suining Central Hospital Neurology Department. All the individuals completed the Parkinson's Disease Cognitive Rating Scale (PD-CDR). The Unified Parkinson's Disease Rating Scale part III (UPDRS-III) was employed for measuring the severity of motor symptoms, while the Hoehn-Yahr scale was used to measure the clinical symptom stage. Fasting venous blood samples were also drawn to measure the Hcy concentration, red blood cell folate, and vitamin B12. Results: In this cross-sectional study, 47 (21.5%) patients with PD showed cognitive dysfunction. The serum Hcy levels were significantly higher in the cognitive impairment PD (PDCI) group compared with the cognitive normal PD group (P<0.001). The Generalized Additive Model (GAM) analysis revealed a nonlinear relationship between Hcy and the risk of PDCI. Multiple logistic regression analyses demonstrated a positive relationship between elevated Hcy and the risk of PDCI in the fully adjusted model ([OR]:3.1, 95% CI, 1.1-8.5, P=0.028). Segmented linear regression analysis showed that when Hcy levels were above 17.7 umol/l, the risk of PDCI increased by 1.6 times for every 1 unit elevated in Hcy (95% CI:1.1-2.2, P=0.008). Conclusion: This study revealed a nonlinear positive correlation between the risk of PDCI and elevated serum Hcy levels in early PD patients, suggesting hyperhomocysteinemia as one of the treatable factors for cognitive impairment in the early stages of PD.

An injectable, chitosan-based hydrogel prepared by Schiff base reaction for anti-bacterial and sustained release applications.

Injectable hydrogels, providing sustained release as implanted materials, have received tremendous attention. In this study, chitosan-based hydrogels were prepared via Schiff base reaction of the aldehyde groups on Poly(NIPAM-co-FBEMA) and the amine groups on chitosan. Owing to the dynamic covalent linkage, the SC/PNF hydrogels exhibit pH-responsive, reversible sol-gel transition, injectable, and self-healing capacity. The mechanical strength of SC/PNF hydrogels can be operated simply by switching the composition or solid content of Poly(NIPAM-co-FBEMA) copolymers. Rheological analyses, including frequency sweeps, strain sweep scanning, and dynamic time sweeps, were employed to demonstrate the relationship between storage modulus (G'), loss modulus (G″), and composition of the SC/PNF hydrogels. In vitro release behaviors reveal that vancomycin-loaded SC/PNF hydrogel could contribute to both the initial burst release (over 1000 ppm within 4 h) and the sustained release (3000 ppm for at least 30 days). Pristine SC/PNF hydrogel holds good biocompatibility toward L929 cells and S. aureus that it degrades as incubated with S. aureus. However, vancomycin-wrapped SC/PNF hydrogel possesses a rapid bacterial-killing effect with a clear inhibition zone. In short, the SC/PNF hydrogels deliver not only sustainable release ability but also tunable physical properties, which are expected to be an outstanding candidate for non-invasive, anti-infection applications.

Development of fixed-point two-degree-of-freedom angular error measurement system with precision improvement function.

In the field of precision industries, measuring micro-angular errors plays a crucial role in improving the accuracy of equipment. Therefore, this study aims to develop a two-degree-of-freedom (two-DOF) angular error measurement system for simultaneously measuring the assembly angle errors of the bond head in a die bonding machine. This system is based on the laser collimation method and constructed by using components such as a fiber laser and position-sensitive detectors. It utilizes the angular drift compensation of the laser beam and averaging function to improve the measurement accuracy. In addition, the mathematical model of the proposed system was established by using skew-ray tracing. Through experiments, the measuring accuracy of ±0.25 arcsec and measuring repeatability of 0.3 arcsec could be achieved.

Prevalence, proportions of elevated liver enzyme levels, and long-term cardiometabolic mortality of patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIM: This study estimated the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) according to cardiometabolic risk factors. The long-term impacts of MASLD on all-cause and cardiometabolic-specific mortality were evaluated. METHODS: We enrolled 343 816 adults aged ≥30 years who participated in a health screening program from 1997 through 2013. MASLD was identified on the basis of abdominal ultrasonography and metabolic profiles. The participants were further categorized by liver enzyme elevation. Baseline cardiometabolic comorbidities were classified on the basis of self-reported medication use and clinical seromarkers. All-cause and cardiometabolic-specific deaths were determined through computerized data linkage with nationwide death certifications until December 31, 2020. RESULTS: The overall prevalence of MASLD was 36.4%. Among patients with MASLD, 35.9% had abnormal liver enzyme levels. Compared with patients without MASLD, abnormal liver enzymes were positively associated with cardiometabolic comorbidities in patients with MASLD (Pfor trend < 0.001). After follow-up, patients with MASLD had a 9%-29% higher risk of all-cause, cardiovascular-related, or diabetes-related mortality. In the groups with MASLD and elevated and normal liver enzyme levels, the multivariate-adjusted hazard ratios for cardiovascular deaths were 1.14 (1.05-1.25) and 1.10 (1.03-1.17), respectively, and those for diabetes deaths were 1.42 (1.05-1.93) and 1.24 (0.98-1.57), respectively, compared with those in the non-MASLD group (Pfor trend < 0.001). DISCUSSION: Individuals with MASLD and elevated liver enzyme levels exhibited significantly higher risks of all-cause and cardiometabolic deaths and should be monitored and given consultation on cardiometabolic modifications.

Gut microbiota-bile acid axis mediated the beneficial associations between dietary lignans and hyperuricemia: a prospective study.

Background: The escalating prevalence of hyperuricemia is emerging as a significant public health concern. The association between dietary lignans and hyperuricemia is yet to be fully elucidated. Our study aims to evaluate the relationships between dietary lignan intake and hyperuricemia among middle-aged and elderly Chinese individuals, with an additional focus on investigating the underlying mechanisms. Methods: Dietary lignan intake was measured using a validated Food Frequency Questionnaire in 3801 participants at the baseline. Among them, 2552 participants were included in the longitudinal study with a median follow-up of 10.5 years. The gut microbiota was analyzed by shotgun metagenome sequencing in 1789 participants, and the targeted fecal metabolome was determined in 987 participants using UPLC-MS/MS at the midpoint of follow-up. Results: The multivariable-adjusted HRs (95% CIs) for hyperuricemia incidence in the highest quartile (vs. the lowest quartile) of dietary intake of total lignans, matairesinol, pinoresinol, and secoisolariciresinol were 0.93 (0.78-1.10), 0.77 (0.66-0.90), 0.83 (0.70-0.97), and 0.85 (0.73-1.00), respectively. The gut microbial and fecal metabolic compositions were significantly different across the dietary lignan groups and the hyperuricemia groups. The beneficial associations between dietary lignans and hyperuricemia might be mediated by several gut microbes (e.g., Fusobacterium mortiferum and Blautia sp. CAG-257) and the downstream bile acid products (e.g., NorCA, glycochenodeoxycholic acid, and glycoursodeoxycholic acid). Conclusion: We found that dietary lignans were inversely associated with hyperuricemia incidence, and the gut microbiota-bile acid axis might mediate this association. Our findings provide new perspectives on precise therapeutic targets and underlying mechanisms for conditions associated with elevated uric acid.

Shuganning Injection Suppresses Apoptosis for Protecting Against Cantharidin-Induced Liver Injury by Network Pharmacology and Experiment Validation.

Cantharidin (CTD) is a compound of mylabris with antitumor activity, and CTD can potentially cause toxicity, especially hepatotoxicity. The classical Traditional Chinese Medicine prescription Shuganning injection (SGNI) exerts notable anti-inflammatory and hepatoprotective effects. However, the protective property and mechanism of SGNI against CTD-induced liver injury (CTD-DILI) have not yet been elucidated. To investigate the effective compounds, potential targets, and molecular mechanism of SGNI against CTD-DILI, network pharmacology combined with experiments were performed. This study found that SGNI could act with 62 core therapeutic targets, regulate multiple biological processes such as apoptosis, and oxidative stress, and influence apoptotic and p53 signaling pathways to treat CTD-DILI. Subsequently, HepaRG cell experiments demonstrated that SGNI pretreatment significantly increased the levels of GSH-Px and SOD, inhibiting the apoptosis induced by CTD. In vivo, according to H&E staining, SGNI can reduce the degeneration of hepatocytes and cytoplasmic vacuolation in mice exposed to CTD. Western blot analysis results indicated that SGNI pretreatment significantly suppressed the expressions of Caspase-3 and Bax while increasing the expression of Bcl-2. In conclusion, SGNI acted as a protective agent against CTD-DILI by inhibiting apoptosis.