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This study aimed to investigate the correlation between the Hemoglobin-to-Red Blood Cell Distribution Width Ratio (HRR) and Peripheral Artery Disease (PAD) prevalence, utilizing data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004. The study employed a cross-sectional design, analyzing data from 5,196 participants aged 40 and above. PAD was diagnosed using the Ankle-Brachial Index (ABI), with ABI less than 0.9 indicating PAD. HRR, calculated as the ratio of hemoglobin (HB) to red blood cell distribution width (RDW), was stratified into quartiles. Covariates included demographic and clinical variables such as BMI, lipid profiles, and diabetes status. Logistic regression analysis was conducted to assess the relationship between HRR and PAD, adjusting for potential confounders. The study found that higher HRR quartiles were associated with a decreased risk of PAD. After adjusting for confounders, the odds ratios for PAD in relation to the second, third, and fourth quartiles of HRR compared to the first quartile were 0.71, 0.62, and 0.44, respectively (P < 0.001). A one-unit increase in HRR corresponded to a 56% reduction in the probability of PAD. ROC analysis indicated HRR as a stronger protective factor for PAD compared to other variables. Stratified analyses revealed that younger age and lower BMI amplified the protective effect of HRR on PAD. The study demonstrated a significant inverse relationship between HRR and PAD, suggesting that HRR may serve as a protective factor against PAD. This finding highlights the potential role of HRR in the pathogenesis of PAD and its clinical implications.

Background Several immune checkpoint inhibitors have been implemented for cancer treatment which have shown some degree of antitumor effcacy, while immune-related adverse events (irAEs) that affect multiple organ functions ensue which obviously should not be neglected. Though less common than other kinds of irAEs, Immune checkpoint inhibitors (ICIs) related Isolated ACTH deficiency (IAD) may cause long-term damage to pituitary-adrenal axis. Several case reports are available about IAD during anti-PD-1 therapy. We report the first case of immune checkpoint inhibitor-induced IAD following 3 month of sintilimab therapy. Case presentation A 66-year-old Chinese man was diagnosed with stage IIIB lung adenocarcinoma with involving ipsilateral intrapulmonary and hilar lymph node metastasis. After 3 months of combination therapy of nedaplatin, pemetrexed and sintilimab, the patient presented with general fatigue, nausea and vomiting. Laboratory investigation at admission revealed hyponatremia and hypokalemia. Further investigation revealed adrenocorticotropic hormone and cortisol levels were far below than normal limits. His other pituitary hormone levels were normal, except for mild elevation of follicle stimulating hormone and estradiol. Cranic magnetic resonance imaging showed a normal pituitary gland. Isolated adrenocorticotropic hormone deficiency was diagnosed, and corticosteroid replacement therapy was administered, leading to a significant improvement of his symptoms while ACTH level maintaining low level. Conclusions Our patient developed isolated ACTH deficiency during combination cancer treatment with chemotherapy and sintilimab. Although isolated ACTH deficiency due to anti-PD-1 including sintilimab therapy is rare occurrence, it can often cause severe clinical symptoms. Its diagnosis basically relies on clinical symptoms and endocrinological examination. Unlike traditional hypophysitis diagnosed by cranial MRI, pituitary MRI of IAD due to anti-PD-1 often indicates normal pituitary gland implying that over-reliance on imaging findings is not recommended. Even if clinical symptoms have relieved after corticosteroid replacement therapy was commenced, low levels of ACTH or cortisol could maintain for a long period which highlights the need for long term corticosteroid therapy. The purpose of the current report was to provide increased awareness of early detection and therapy of IAD.

Backgrounds: Psoraleae Fructus (PF)-induced hepatotoxicity has been reported in clinical and animal experiments. However, the hepatotoxic constituents and mechanisms underlying PF-induced toxicity have remained unclear. Therefore, this study explored the potentially toxic PF components and revealed their relative mechanisms. Methods: The hepatotoxicity of PF water (PFW) and ethanol (PFE) extracts was compared using Kunming mice. The different compositions between PFW and PFE, which were considered toxic compositions, were identified using the UHPLC-Q-Exactive MS method. Then, L02 and HepG2 cell lines were used to evaluate the toxicity of these compositions. Cell viability and apoptosis were determined through the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. An automatic biochemical analyzer detected the aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Lastly, we used high-content screening (HCS) to determine the levels of reactive oxygen species (ROS), lipid, and mitochondrial membrane potential (MMP). Results: The ethanol extraction process aggravated the hepatotoxicity of PF, causing more severe injuries. The content of psoralen, isopsoralen, bavachin, psoralidin, bavachinin, neobavaisoflavone, and bakuchiol was higher in the PFE than PFW. Bavachin, psoralidin, bavachinin, neobavaisoflavone, and bakuchiol induced cell apoptosis and the AST, ALT, and ALP leakages. Furthermore, these five constituents increased intracellular lipid accumulation and ROS levels but decreased the MMP level. Conclusion: The ethanol extraction process could induce severe PF hepatotoxicity. Bavachin, psoralidin, bavachinin, neobavaisoflavone, and bakuchiol are the main hepatotoxic ingredients. This mechanism could be associated with oxidative stress and mitochondrial damage-mediated apoptosis. Taken together, this study provides a basis for the clinical application of PF that formulates and improves its herbal standards.

Epimedii Folium (EF, Epimedium brevicornu Maxim.), a traditional botanical drug, is famous for treating bone fractures, joint diseases, and several chronic illnesses. However, some studies indicated that EF could induce idiosyncratic drug-induced liver injury (IDILI) in the clinic. The NLRP3 inflammasome plays a crucial role in the pathogenesis of various human diseases, including IDILI. In the present study, we showed that epimedin B could specifically facilitate nigericin- or ATP-induced NLRP3 inflammasome activation under synergistic induction of mitochondrial reactive oxygen species. Moreover, epimedin B resulted in activation of Caspase-1 and IL-1β secretion in a lipopolysaccharide (LPS)-mediated susceptibility mouse model. MCC950 pretreatment completely abrogated activation of the NLRP3 inflammasome and prevented liver injury. Importantly, several studies have confirmed that some active constituents of EF could enhance activation of the NLRP3 inflammasome and may be involved in the pathogenesis of EF-IDILI. No reports are available on whether the structure-activity relationship associated with the immunostimulatory activity in EF contributes to the pathogenesis of EF-IDILI. These findings have changed our conventional understanding about the more glycogen, the more immunostimulatory activity.

Background Psoralea corylifolia (PF) is widely utilized for the treatment of conditions such as kidney yang deficiency, frequent urination, and cold pain in the waist and knees. However, both basic research and clinical reports indicate that it induce hepatotoxicity. Our preliminary research has confirmed that PF has hepatotoxicity and in vitro research indicated that psoralidin is hepatotoxic. but it remains unclear whether psoralidin is the hepatotoxic component of PF and the mechanism of psoralidin induces hepatotoxicity. This study aimed to investigate the hepatotoxicity induced by psoralidin and its toxic mechanisms. Methods Kunming mice were used to conduct long-term toxicity experiments. Liver function indices, organ coefficients, and histopathological observations were employed to assess the hepatotoxicity of psoralidin. Non-targeted metabolomics and proteomics analyses were conducted to elucidate the potential pathways and targets associated with psoralidin-induced hepatotoxicity. Furthermore, immunofluorescence staining, molecular docking and Western blotting analyses were utilized to validate the mechanisms underlying psoralidin hepatotoxicity. Results The elevation of ALT and AST, accompanied by hepatic steatosis and lipid droplet aggregation were observed after psoralidin treatement. Psoralidin affected biosynthesis of unsaturated fatty acid, fatty acid metabolism, arachidonic acid metabolism, phospholipid metabolism, and oxidative phosphorylation. Further validation research found that psoralidin induced the expressions of Acot4 and Plin5, which in turn caused up-regulations of TGs and FFA in mice, and increased the HSD17B12 level, thereby promoting the synthesis of long-chain fatty acids and facilitating lipid synthesis. And psoralidin catalyzed the conversion of phosphatidylcholine into LPC by enhancing Pla2g6 and Pla2g12b levels, which promoted the synthesis and accumulation of TGs, ultimately inducing disorders in glycerophospholipid metabolism. Furthermore, psoralidin caused upregulation of ROS and mitochondrial damage, leading to a decrease in FA oxidation. Conclusion Psoralidin is one of the hepatotoxic components of PF, which induced hepatotoxicity via promoting lipid synthesis and inhibiting lipid oxidative degradation. Graphical Abstract

In the field of ocean engineering, the variation of flow field during ship-to-ship (STS) interaction has been a hot topic. Noteworthy, the effect of vortex distribution on flow field characteristic variations during STS interaction remains insufficiently researched. This study modifies the RNG k-ε model using the OpenFOAM platform and verifies its reliability by comparing it with literature data. Subsequently, extended research is conducted to investigate the flow field characteristics of two different ship hull sections under different Reynolds numbers (Re=68,000 and Re=6800), analyzing velocity components, vortex distribution, and trends in pressure and turbulent kinetic energy fields relative to the vortex field. The research reveals that Re primarily governs changes in upstream and downstream flow fields, while in the gap field, the variation in flow field characteristics is more constrained by geometry and boundary conditions. This research provides a valuable reference for assessing flow field characteristics in STS interactions.

Background Registry-based data on the long-term survival of ANCA-associated vasculitis (AAV) patients on maintenance hemodialysis (MHD) in China are limited, particularly across the COVID-19 pandemic period. Methods Data were obtained from the Wuhan Dialysis Registry (2017–2025), including 9,430 MHD patients with complete data, of whom 54 (0.57%) had AAV. Propensity score matching (1:3) generated 54 AAV and 162 non-AAV patients. All-cause survival was compared using Kaplan-Meier methods. Cox proportional hazards models were used to evaluate mortality risk factors among AAV patients. Results Overall survival was comparable between AAV and matched non-AAV patients. 1-, 2-, 3-, and 5-year survival rates were 91.8%, 84.2%, 75.2%, and 67.5% in AAV, versus 94.5%, 85.5%, 81.2%, 67.7% in non-AAV patients ( P  = 0.737). Among 12 deaths in AAV patients (median age 74.0 years, median dialysis vintage 21.0 months), infection was the leading cause (8/12, 66.7%), including COVID-19 in 3 cases (25.0%); no deaths were attributed to AAV relapse. Univariable Cox regression identified that older age (HR 1.09, P  = 0.028), lower hemoglobin (HR 0.96, P  = 0.041), and central venous catheter use (HR 4.01, P  = 0.038) were significantly associated with increased mortality in AAV patients. Multivariable analysis was not performed due to limited events ( n  = 12). Conclusions In this registry-based cohort, overall survival was comparable between AAV and non-AAV patients on maintenance hemodialysis. Infection was the leading cause of death, with no deaths attributed to AAV relapse. These findings highlight the critical importance of infection prevention strategies in this vulnerable population.

To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood urea nitrogen (BUN), cystatin C (Cys-C), 24-hour urinary protein (24 h Upro)], oxidative stress markers [malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS)], inflammatory factors [C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6)], and adverse reactions were compared between groups. The cumulative treatment effectiveness (defined as the sum of patients with \"markedly effective\" and \"effective\" outcomes) was significantly higher in the observation group (92.45%) compared to the control group (78.43%, P<0.05). Post-treatment, the observation group demonstrated significantly greater improvements in all parameters: lower BUN (4.35±1.06 vs 5.29±1.12 mmol/L), Cys-C (1.21±0.34 vs 1.75±0.46 mg/L), 24 h Upro (66.79±18.37 vs 75.17±19.54 mg/24h), MDA (3.54±0.89 vs 4.63±1.08 nmol/mL), ROS (371.34±46.32 vs 417.53±48.16 U/mL), CRP (5.02±0.83 vs 6.63±0.94 mg/L), IL-1β (11.04±2.38 vs 13.61±2.67 pg/mL), and IL-6 (12.78±3.51 vs 16.84±4.53 pg/mL), alongside higher SOD (88.17±9.34 vs 72.49±8.71 U/mL) (P<0.05). Adverse reaction incidence showed no significant difference (16.98% vs 13.73%, P>0.05). In ESDN patients, the combination of Levocarnitine and Alprostadil demonstrates superior cumulative treatment effectiveness over Alprostadil monotherapy in improving renal function, reducing oxidative stress, and attenuating inflammation, without increasing the incidence of adverse reactions.

Objective: The relationship between different types of vascular access in maintenance hemodialysis (MHD) patients and patient prognosis is controversial. The vascular access of patients from various dialysis centers in Wuhan was summarized, and its relationship with prognosis was analyzed. Methods: The characteristics of MHD patients treated at 70 dialysis centers in the Wuhan Hemodialysis Quality Control System from 2017 to 2023 were collected. The demographic characteristics, laboratory indicators, compliance rates with laboratory indicators, annual mortality changes, survival time, and risk of death were compared in patients with various types of vascular access. Results: A total of 45,830 MHD patients were included in the study. Overall, arteriovenous fistulas (AVFs) and tunneled and cuffed catheters (TCCs) remain the most common types of vascular access. Non‐tunneled and cuffed catheters (NCC) use decreases annually, whereas arteriovenous graft (AVG) use increases annually. Male patients mostly had AVFs. The vascular access types of patients with diabetic nephropathy were mainly TCCs (28.6%) and AVGs (29.4%). AVG patients had the highest average hemoglobin level. NCC patients had the lowest average hemoglobin, albumin, and potassium levels. AVF patients had the highest average albumin, potassium, calcium, phosphorus, and parathyroid hormone levels. TCC patients had the lowest calcium and phosphorus levels. From 2017 to 2023, the mortality rates of AVF, TCC, and AVG patients were significantly higher in 2022 (11%, 19.9%, and 11.7%, respectively). The median survival time of AVF patients was 4.92 (2.75, 7.75) years, which was significantly longer than that of TCC patients (2.83 [1.42, 4.92]) and NCC patients (1.00 [0.25, 2.25]). After multivariate adjustment, the risk of death in patients with internal fistulas was 50.6% lower than that in patients with catheters, according to the Cox regression analysis model (hazard ratio = 0.494, 95% CI: 0.439–0.556, p < 0.001). Conclusions: Among MHD patients with different vascular access types who were treated in Wuhan from 2017 to 2023, the numbers of AVF, AVG, and TCC patients increased with increasing overall number of MHD patients, whereas the number of NCC patients decreased. The overall condition and survival time of AVF patients were significantly better than those of MHD patients with other vascular access types, and the risk of death was lower.

The main constituents of a typical medicinal herb, Polygonum multiflorum （Heshouwu in Chinese）, that induces idiosyncratic liver injury remain unclear. Our previous work has shown that cotreatment with a nontoxic dose of lipopolysaccharide （LPS） and therapeutic dose of Heshouwu can induce liver injury in rats, whereas the solo treatment cannot induce observable injury. In the present work, using the constituent ＂knock-out＂ and ＂knock-in＂ strategy, we found that the ethyl acetate （EA） extract of Heshouwu displayed comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Results indicated a significant elevation of plasma alanine aminotransferase, aspartate aminotransferase, and liver histologic changes, whereas other separated fractions failed to induce liver injury. The mixture of EA extract with other separated fractions induced comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Chemical analysis further revealed that 2,3,5,4＇-tetrahydroxy trans-stilbene-2-O-p-glucoside （trans-SG） and its cis-isomer were the two major compounds in EA extract. Furthermore, the isolated cis-, and not its trans-isomer, displayed comparable idiosyncratic hepatotoxicity to EA extract in LPS-treated rats. Higher contents of cis-SG were detected in Heshouwu liquor or preparations from actual liver intoxication patients associated with Heshouwu compared with general collected samples. In addition, plasma metabolomics analysis showed that cis-SG-disturbing enriched pathways remarkably differed from trans-SG ones in LPS-treated rats. All these results suggested that cis-SG was closely associated with the idiosyncratic hepatotoxicity of Heshouwu. Considering that the cis-trans isomerization oftrans- SG was mediated by ultraviolet light or sunlight, our findings serve as reference for controlling photoisomerization in drug discovery and for the clinical use of Heshouwu and stilbene-related medications.