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Paget's disease of the perianal skin (PPD) is a rare form of extramammary Paget's disease, which can manifest as either a primary intraepithelial adnexal neoplasm or as a secondary condition resulting from the spread of an underlying colorectal lesion. Surgical resection is the primary treatment for PDD, but it poses risks to the aesthetic appearance and functional integrity of the anus. Moreover, its clinical application is limited, particularly in cases of lesions present in multiple skinfold areas, multiple and recurrent lesions, extensive lesion areas, or in elderly patients with poor health. Hematoporphyrin derivative photodynamic therapy (HpD-PDT) serves as an alternative treatment for patients who are not suitable candidates for surgery and for conditions characterized by extensive and discontinuous disease. Here, we present the case of a 70-year-old man with PPD, presenting perianal skin lesions extending beyond the dentate line into the anal canal. When considering HpD-PDT, it is essential to take into account the preservation of function, patient preferences, and potential adverse effects. Subsequent to HpD-PDT, the lesion was effectively eradicated, and anal function was preserved without any notable proliferative, atrophic scarring, or other side effects. Therefore, HpD-PDT proves to be an effective treatment for PPD, offering aesthetic improvement, minimal functional disruption, and a high level of tolerability.

To investigate the role and possible mechanisms of tetrathiomolybdate (TTM) in ovariectomy (OVX)-induced osteoporotic mice. Eighteen 12-week-old C57BL/6 female mice were randomized into three groups: sham-operated group (Sham group, n = 6), OVX-induced osteoporosis (OP) group (OP group, n = 6), and OVX-induced OP+TTM gavage-treated group (OP+TTM group, n = 6). The mice body weight results and abdominal fat macroscopic view showed significant improvement in obesity in the OP+TTM group of mice as compared to those in the OP group. HE staining and micro-CT scanning results demonstrated that mice in the OP+TTM group showed milder bone loss than those in the OP group. The results of TRAP staining also supported these findings. In addition, serum lipid profiling and immunohistochemical staining showed that compared with mice in the OP group, mice in the OP+TTM group had significantly lower serum levels of triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), as well as PPARγ and FABP4 protein expression in the femur. Further, the results of transcriptome sequencing analysis indicated that the differential genes between OP+TTM and OP groups were mainly enriched in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Immunofluorescence assay preliminarily confirmed that the expression of p-PI3K and p-Akt proteins was significantly elevated in the femur of mice in the OP+TTM group, especially in the bone marrow cavity. Taken together, we reported for the first time that TTM ameliorated obesity and inhibited bone loss in OP mice, which may be related to the activation of PI3K/Akt signaling.

Background: Overtime work is common in anesthesiologists due to shortage of manpower. Herein, we analyzed if overtime work of anesthesiologists was associated with delirium development in older patients after surgery., Methods: This was a secondary analysis of the database from a randomized trial. Seven hundred older patients (aged ≥ 65 years) who were admitted to the intensive care unit (ICU) after elective noncardiac surgery were enrolled in the underlying trial. Anesthesiologists who worked continuously for more than 8 h by the end of the surgery were marked as "work overtime". Delirium was assessed with the Confusion Assessment Method for the ICU twice daily during the first 7 postoperative days. The association between overtime work of anesthesiologists and development of postoperative delirium was analyzed with multivariable logistic regression models., Results: All 700 patients (mean age 74.3 years, 39.6% female) were included in this analysis. Anesthesiologists of 281 patients (40.1%) were marked as "work overtime" at the end of surgery. When compared with patients whose anesthesiologists didn't work overtime, patients whose anesthesiologist worked overtime had a higher incidence of delirium within 7 days (20.3% [57/281] vs. 12.9% [54/419], P = 0.009). After correction for confounding factors, both overtime work (OR 1.87, 95% CI 1.19-2.94, P = 0.007) and prolonged continuous working hours of anesthesiologists (OR 1.08, 95% CI 1.01-1.15, P = 0.020) were associated with an increased risk of postoperative delirium., Conclusions: Overtime work of anesthesiologists was associated with an increased risk of delirium development in older patients admitted to ICU after major noncardiac surgery., Trial Registration: The underlying trial was registered with Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=8734 ; ChiCTR-TRC-10000802; March 18, 2010)., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Biomedical Research Ethics Committee of Peking University First Hospital on October 27, 2022 (2022[470]). Ethical approval for the original study was provided by the Clinical Research Ethics Committee of Peking University First Hospital (Chairperson Prof Guo Xiaohui) and registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-10000802). Participants or their legal representatives were provided informed consent prior to enrollment into the original study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Poor oral health, prevalent among the older adults, can undermine overall health and contribute to frailty. Older adults experiencing oral frailty and dysbiosis potentially face an elevated risk of postoperative delirium. This study aims to explore the influence of oral frailty and changes in oral microbiota composition on occurrence of postoperative delirium in older adult patients undergoing non-cardiac surgery., Methods: A total of 303 older adult patients undergoing non-cardiac surgeries were recruited in the Second Affiliated Hospital of Nanjing Medical University from July 2023 to December 2023. Oral swabs for oral microbiota analyses were collected before surgery. Subsequently, after propensity score matching, 21 samples from patients with postoperative delirium and 21 samples from patients without postoperative delirium were analyzed for oral microbiota. Our primary objective was to determine the association between oral frailty, changes in oral microbiota composition, and the occurrence of postoperative delirium., Results: Oral frailty emerged as an independent risk factor for postoperative delirium [HR = 1.75; 95% CI = (1.04-2.96); p = 0.035]. Additionally, patients with postoperative delirium demonstrated lower oral microbiota diversity, as indicated by a reduced Chao index compared with those without postoperative delirium (p = 0.034). A significant association was also found between the dysbiosis index and postoperative delirium (p < 0.001). ROC analysis revealed a pronounced area under the curve of 0.95 (95% CI: 0.88-1.00) for the dysbiosis index in predicting postoperative delirium. Subsequent Principal Coordinates and Kaplan-Meier analyses affirmed that both beta diversity and the dysbiosis index were significantly correlated with incidence of postoperative delirium, with p-values of 0.002 and <0.001, respectively. Furthermore, the interaction analysis through Cox proportional hazards regression suggested a combined effect of oral frailty and the dysbiosis index on the likelihood of developing postoperative delirium (p = 0.004)., Conclusions: Oral frailty and changes in oral microbiota among older adult patients undergoing non-cardiac surgery may influence the incidence of postoperative delirium., (© 2024 The American Geriatrics Society.)

To analyze the role of disulfidptosis in ulcerative colitis (UC), large-scale datasets combined with weighted gene co-expression network analysis (WGCNA) and machine learning were utilized and analyzed. When the hub genes that are associated with UC disease phenotypes and have predictive performance were identified, immune cell infiltration and the CeRNA network were constructed, the role of hub genes in UC pathogenies and biotherapy were investigated, and molecular docking studies and mice-verified tests were carried out to further explore the potential core genes and potential target. Finally, we found 21 DRGs involved in UC pathogenesis, including SLC3A2, FLNA, CAPZB, TLN1, RPN1, etc. Moreover, SLC3A2, TLN1, and RPN1 show a notable correlation with UC inflammatory state, and the expression of DRGs is closely related to the response to UC biotherapy. Our study suggests that disulfidptosis plays a crucial role in the pathogenesis and disease progression of UC. Higher expression of DRGs is commonly observed in moderate to severe UC patients, which may also affect their response to biologic therapies. Among the identified genes, SLC3A2 stands out, providing new insights into the underlying mechanisms of UC and potentially serving as a novel therapeutic target for the treatment of UC.

Background: Dexmedetomidine may improve sleep quality after surgery, but conflicting results also exist. Herein, we explored the effects of perioperative dexmedetomidine on postoperative sleep quality in adult patients., Methods: In this systematic review and meta-analysis, randomized controlled trials investigating the effects of perioperative dexmedetomidine on sleep quality after noncardiac surgery were retrieved from Cochrane Library, PubMed, and EMBASE from inception to January 12, 2023, and updated on March 15, 2024. The Cochrane Collaboration's tool was applied to assess risk of bias. A random-effects model was used for meta-analysis. The primary outcome was the subjective sleep quality score on the first night after surgery., Results: A total of 29 trials containing 5610 participants were included. The subjective sleep score on the first postoperative night was lower (better) with dexmedetomidine than with placebo (SMD [standardized mean difference] = -0.8, 95% CI -1.1 to -0.6, p<0.00001; I2 = 93%; 22 trials; n = 4611). Sensitivity analysis showed that overall conclusion was not changed (SMD = -0.8, 95% CI -1.1 to -0.5, p<0.00001; I2 = 93%; 14 trials; n = 3846). Results of polysomnographic monitoring showed improved sleep structure with dexmedetomidine on the first night after surgery, as manifested by increased sleep efficiency index and stage N2 sleep and decreased arousal index and stage N1 sleep., Conclusions: This systematic review suggests that, among patients who underwent noncardiac surgery, perioperative dexmedetomidine administration may improve early postoperative sleep quality pattern. However, the resulting evidence were of low or very low qualities and further studies are required to confirm our results., Prospero Registration Number: CRD42023390972., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Posttraumatic stress disorder (PTSD) is associated with the development of dementia. However, the link between PTSD and preclinical Alzheimer's disease pathology (amyloid β [Aβ]) remains controversial. Moreover, the correlation between the severity of PTSD with Aβ levels remains unknown., Methods: This cross-sectional study sought to investigate the associations of PTSD symptoms with global and regional brain Aβ burden. To this end, data were obtained from participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Study. In addition, we explored the association between the severity of PTSD symptoms and Aβ levels., Results: A total of 4,228 participants aged 65 to 85 years were included in the final analysis. The results showed that PTSD symptoms were significantly associated with higher global Aβ levels (1.15 ± 0.20 vs. 1.09 ± 0.19; β = 0.056; p  < 0.001), after adjusting for covariates. The association between PTSD symptoms and Aβ levels was not affected by sex, age, ApoE genotype, or psychiatric diseases. Similarly, PTSD symptoms were significantly associated with Aβ levels in all subregions, including the anterior cingulate, posterior cingulate, parietal cortex, precuneus, temporal cortex, and frontal cortex. In addition, the group with severe PTSD symptoms (1.22 ± 0.24) exhibited higher global Aβ levels than the groups with moderate (1.14 ± 0.19) or mild (1.12 ± 0.20) symptoms or the control (1.08 ± 0.18), with p  < 0.001., Conclusion: The findings imply a close relationship between PTSD and brain Aβ levels, irrespective of sex, age, ApoE genotype, or psychiatric diseases. More well-designed studies are needed to further explore the relationship and mechanism underlying the association between PTSD and Aβ burden., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Gong, Wang, Shi, Li, Wen, Wang, Zheng and Han.)

Study Objective: To test the hypothesis that emergence delirium might be associated with worse long-term survival., Design: A longitudinal prospective observational study., Setting: A tertiary hospital in Beijing, China., Patients: A total of 942 patients aged 65-90 years who were admitted to post-anesthesia care unit (PACU) after major noncardiac surgery under general anesthesia., Exposures: Emergence delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit during PACU stay., Measurements: Patients were followed up once a year for at least 3 years. Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals. Associations between emergence delirium and long-term survivals were analyzed with the Cox proportional hazard models., Main Results: Among enrolled patients, 915 completed perioperative assessments; 906 completed long-term follow-up (mean age 72 years; 60 % [545/906] male; 73 % [660/906] cancer surgery). At the end of follow-up (median 43 months), there were 69 deaths in 331 patients (21 %) with emergence delirium versus 114 deaths in 575 patients (20 %) without: unadjusted hazard ratio 1.10 (95 % CI: 0.81 to 1.48); P = 0.547; adjusted hazard ratio 0.96 (95 % CI: 0.70 to 1.32); P = 0.797. Recurrence-free survival was 73/331 (22 %) in patients with emergence delirium versus 121/575 (21 %) without: unadjusted hazard ratio 1.08 (95 % CI: 0.81 to 1.45); P = 0.598; adjusted hazard ratio 0.94 (95 % CI: 0.69 to 1.28); P = 0.695. Event-free survival was 159/331 (48 %) in patients with emergence delirium versus 268/575 (47 %) without: unadjusted hazard ratio 1.06 (95 % CI: 0.87 to 1.29); P = 0.563; adjusted hazard ratio 0.98 (95 % CI: 0.80 to 1.21); P = 0.875., Conclusions: We did not find significant association between emergence delirium and worse long-term survival in older patients after general anesthesia and major surgery mainly for cancer. The effects of emergence delirium on long-term outcomes deserve further investigation., Clinical Trial Registrations: www.chictr.org.cn; ChiCTR-OOC-17012734., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Propofol is commonly used for procedural sedation but may increase side effects in a dose-dependent manner. Remimazolam, an ultrashort-acting benzodiazepine, has been approved for procedural sedation but may delay awakening. This study tested the hypothesis that remimazolam as a supplement reduces effect-site propofol concentration (Ce prop ) required to suppress response to cervical dilation in patients undergoing hysteroscopy., Methods: One hundred and fifty patients who were scheduled for hysteroscopy were randomized to receive 0, 0.05, 0.1, 0.15, or 0.2 mg·kg -1 intravenous remimazolam, followed by a bolus of sufentanil 0.15 μg⋅kg -1 , and a target-controlled propofol infusion. The initial target Ce prop was 3.5 μg·mL -1 and was increased or decreased in subsequent patients by steps of 0.5 μg·mL -1 according to whether there was loss of response to cervical dilation in the previous patient. We used up-down sequential analysis to determine values of Ce prop that suppressed response to cervical dilation in 50% of patients (EC 50 )., Results: The EC 50 of propofol for suppressing response to cervical dilation was lower in patients given 0.1 mg·kg -1 (2.08 [95% confidence interval, CI, 1.88-2.28] μg·mL -1 ), 0.15 mg⋅kg -1 (1.83 [1.56-2.10] μg·mL -1 ), and 0.2 mg⋅kg -1 (1.43 [1.27-1.58] μg·mL -1 ) remimazolam than those given 0 mg⋅kg -1 (3.67 [3.49-3.86] μg·mL -1 ) or 0.05 mg⋅kg -1 (3.47 [3.28-3.67] μg·mL -1 ) remimazolam (all were P < .005). Remimazolam at doses of 0.1, 0.15, and 0.2 mg·kg -1 decreased EC 50 of propofol by 43.3% (95% CI, 41.3%-45.5%), 50.3% (48.0%-52.8%), and 61.2% (58.7%-63.8%), respectively, from baseline (remimazolam 0 mg⋅kg -1 ). Propofol consumption was lower in patients given 0.1 mg⋅kg -1 (4.15 [3.51-5.44] mg·kg -1 ), 0.15 mg⋅kg -1 (3.54 [3.16-4.46] mg·kg -1 ), and 0.2 mg⋅kg -1 (2.74 [1.73-4.01] mg·kg -1 ) remimazolam than those given 0 mg⋅kg -1 (6.09 [4.99-7.35] mg·kg -1 ) remimazolam (all were P < .005). Time to anesthesia emergence did not differ significantly among the 5 groups., Conclusions: For women undergoing hysteroscopic procedures, remimazolam at doses from 0.1 to 0.2 mg·kg -1 reduced the EC 50 of propofol inhibiting response to cervical dilation and the total propofol requirement. Whether the combination could improve perioperative outcomes deserves further investigation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Background: Acute kidney injury (AKI) is common after cytoreduction surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for peritoneal surface malignancies. Herein we analyzed the association between intraoperative hyperthermia and AKI following CRS-HIPEC., Methods: In this retrospective cohort study, we collected baseline and perioperative data from patients who underwent CRS-HIPEC mainly for pseudomyxoma peritonei between 2014 and 2020. Nasopharyngeal temperature was recorded at 5-min intervals. The area above the threshold was calculated for intraoperative hyperthermia (>37.0 °C). AKI was diagnosed and classified according to the KDIGO creatinine criteria. A multivariable logistic regression model was established to assess the association between hyperthermia and AKI., Results: A total of 480 patients were included in the analysis. Of these, 10.6% (51/480) developed AKI within 7 postoperative days. After correction for confounding factors, a larger area above the threshold of hyperthermia was significantly associated with an increased risk of AKI (odds ratio [OR] 1.36, 95% CI 1.14-1.63, p  = 0.001). Among other factors, older age (OR 1.05, 95% CI 1.02-1.09, p  = 0.002), postoperative hypotension requiring vasopressors (OR 2.09, 95% CI 1.02-4.27, p  = 0.042), and intraperitoneal chemotherapy containing cisplatin (OR 2.75, 95% CI 1.20-6.33, p  = 0.017) were also associated with an increased risk of AKI. Patients with AKI required longer mechanical ventilation, stayed longer in the intensive care unit and hospital, developed more complications, and required more intensive care unit readmission., Conclusions: Among patients undergoing CRS-HIPEC, intraoperative hyperthermia was independently associated with a higher risk of AKI; this effect was additive to other risk factors including cisplatin-containing chemotherapy.

Backgrounds: There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer., Methods: Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest., Results: Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P < .05)., Conclusion: ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings., (© The Author(s) 2024. Published by Oxford University Press.)

Biocatalysis is an attractive approach for the synthesis of chiral pharmaceuticals and fine chemicals, but assessing and/or improving the enantioselectivity of biocatalyst towards target substrates is often time and resource intensive. Although machine learning has been used to reveal the underlying relationship between protein sequences and biocatalytic enantioselectivity, the establishment of substrate fitness space is usually disregarded by chemists and is still a challenge. Using 240 datasets collected in our previous works, we adopt chemistry and geometry descriptors and build random forest classification models for predicting the enantioselectivity of amidase towards new substrates. We further propose a heuristic strategy based on these models, by which the rational protein engineering can be efficiently performed to synthesize chiral compounds with higher ee values, and the optimized variant results in a 53-fold higher E-value comparing to the wild-type amidase. This data-driven methodology is expected to broaden the application of machine learning in biocatalysis research., (© 2024. The Author(s).)

Objective: To investigate whether Parathyroid hormone (PTH) can promote mandibular distraction osteogenesis by regulating macrophage polarization and the underlying mechanisms of this phenomenon., Methods: Forty-eight Rabbits were used to establish the mandibular distraction osteogenesis experimental model, randomly divided into 2 groups. Intermittent post-operative injections of 20 μg/kg PTH and normal saline were administered to the experimental and control groups, respectively. Regenerated new bone was examined using HE staining, osteoclast numbers were determined through tartrate-resistant acid phosphatase (TRAP) staining, and macrophage polarization markers arginase 1 (Arg1) and inducible nitric oxide synthase (iNOS) expressions were elucidated using immunohistochemistry (IHC), the mRNA expression of CD206, CD11C, Arg1 and iNOS were detected using qPCR., Results: The bone trabeculae in the experimental group were thicker, with a more homogeneous structure and more new osteoid than in the control group. In the area of distraction osteogenesis, the osteoclast count in the experimental group was higher than in the control group ( P   <   0.05 ). IHC results indicated differential expressions of Arg1 and iNOS in the experimental group compared to the control group ( P   <   0.05 ). Relative mRNA expressions of CD11c and iNOS were lower in the experimental group than in the control group ( P   <   0.05 ), whereas the expressions of CD206 and Arg1 mRNA were higher in the experimental group compared to the control group ( P   <   0.05 )., Conclusion: Intermittent PTH injections increased macrophage quantity in the mandible generated by distraction osteogenesis, downregulated iNOS, upregulated Arg1, and promoted macrophage polarization from M1 to M2 phenotype, thereby promoting mandibular distraction osteogenesis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Obstructive sleep apnea (OSA) is common in surgical patients and associated with worse perioperative outcomes., Objectives: To investigate the effect of mini-dose dexmedetomidine supplemented analgesia on postoperative sleep quality pattern in patients at high risk of OSA., Design: A pilot randomized, double-blind, placebo-controlled trial., Setting: A tertiary university hospital in Beijing, China., Patients: One hundred and fifty-two adult patients who had a STOP-Bang score ≥3 and a serum bicarbonate level ≥28 mmol/L and were scheduled for major noncardiac surgery between 29 January 2021 and 20 September 2022., Intervention: After surgery, patients were provided with high-flow nasal cannula and randomized in a 1:1 ratio to receive self-controlled opioid analgesia supplemented with either mini-dose dexmedetomidine (median 0.02 μg/kg/h) or placebo. We monitored polysomnogram from 9:00 pm to 6:00 am during the first night., Main Outcome Measures: Our primary outcome was the percentage of stage 2 non-rapid eye movement (N2) sleep. Secondary and exploratory outcomes included other postoperative sleep structure parameters, sleep-respiratory parameters, and subjective sleep quality (Richards-Campbell Sleep Questionnaire; 0-100 score range, higher score better)., Results: All 152 patients were included in intention-to-treat analysis; 123 patients were included in sleep structure analysis. Mini-dose dexmedetomidine supplemented analgesia increased the percentage of stage N2 sleep (median difference, 10%; 95% CI, 1 to 21%; p  = 0.029); it also decreased the percentage of stage N1 sleep (median difference, -10%; 95% CI, -20% to -1%; p  = 0.042). Other sleep structure and sleep-respiratory parameters did not differ significantly between the two groups. Subjective sleep quality was slightly improved with dexmedetomidine on the night of surgery, but not statistically significant (median difference, 6; 95% CI, 0 to 13; p  = 0.060). Adverse events were similar between groups., Conclusion: Among patients at high risk of OSA who underwent noncardiac surgery, mini-dose dexmedetomidine supplemented analgesia may improve sleep quality without increasing adverse events., Clinical Trial Registration: Clinicaltrials.gov, identifier NCT04608331., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Liang, Chen, Ma, Zhang, Shen, Zhu and Wang.)

Study Objective: To assess the association of intraoperative hypotension with long-term survivals in older patients after major noncardiac surgery mainly for cancer., Design: A secondary analysis of databases from three randomized trials with long-term follow-up., Setting: The underlying trials were conducted in 17 tertiary hospitals in China., Patients: Patients aged 60 to 90 years who underwent major noncardiac thoracic or abdominal surgeries (≥ 2 h) in a single center were included in this analysis., Exposures: Restricted cubic spline models were employed to determine the lowest mean arterial pressure (MAP) threshold that was potentially harmful for long-term survivals. Patients were arbitrarily divided into three groups according to the cumulative duration or area under the MAP threshold. The association between intraoperative hypotension exposure and long-term survivals were analyzed with the Cox proportional hazard regression models., Measurements: Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals., Main Results: A total of 2664 patients (mean age 69.0 years, 34.9% female sex, 92.5% cancer surgery) were included in the final analysis. MAP < 60 mmHg was adopted as the threshold of intraoperative hypotension. Patients were divided into three groups according to duration under MAP < 60 mmHg (<1 min, 1-10 min, and > 10 min) or area under MAP <60 mmHg (< 1 mmHg⋅min, 1-30 mmHg⋅min, and > 30 mmHg⋅min). After adjusting confounders, duration under MAP < 60 mmHg for > 10 min was associated with a shortened overall survival when compared with the < 1 min patients (adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.09 to 1.57, P = 0.004); area under MAP < 60 mmHg for > 30 mmHg⋅min was associated with a shortened overall survival when compared with the < 1 mmHg⋅min patients (adjusted HR 1.40, 95% CI 1.16 to 1.68, P < 0.001). Similar associations exist between duration under MAP < 60 mmHg for > 10 min or area under MAP < 60 mmHg for > 30 mmHg⋅min and recurrence-free or event-free survivals., Conclusions: In older patients who underwent major noncardiac surgery mainly for cancer, intraoperative hypotension was associated with worse overall, recurrence-free, and event-free survivals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

It has long been an aspirational goal to create artificial channel structures that replicate the feat achieved by ion channel proteins. Biological ion channels occasionally demonstrate multiple conductance states (known as subconductance), remaining a challenging property to achieve in artificial channel molecules. We report a funnel-shaped single-molecule channel constructed by an electron-deficient macrocycle and two electron-deficient aromatic imide arms. Planar lipid bilayer measurements reveal distinct current recordings, including a closed state, two conducting states, and spontaneous transitions between the three states, resembling the events seen in biological ion channels. The transitions result from conformational changes induced by chloride transport in the channel molecule. Both opening states show a non-linear and rectifying I-V relationship, indicating voltage-dependent transport due to the asymmetrical channel structure. This work could enhance our understanding of ion permeation and channel opening mechanism., (© 2024 Wiley-VCH GmbH.)

Prenylated indole alkaloids, which are mainly produced by genera Aspergillus and Penicillium, are a class of structurally intriguing specialized metabolites with remarkable biomedical interests. In this study, chemically guided isolation of the Nicotiana tabacum-derived endophytic fungus Aspergillus japonicus TE-739D yielded eight structurally diverse prenylated indole alkaloids, including an undescribed compound, namely aspertaichamide B (ATB, 1), together with seven previously discovered derivatives (compounds 2 - 8). Their chemical structures as well as the stereochemical features were determined by integrated spectroscopic analyses, including HRESIMS, NMR, NMR calculations with DP4 + probability analysis, and a comparison of the experimental ECD data with computed DFT-based quantum chemical calculations. In vitro cytotoxic effects against the gastric cancer MFC cells revealed that the new compound ATB demonstrated considerable activity. Further studies found that ATB suppressed the viability, colony formation, and migration ability of MFC cells, and induced MFC cells apoptosis in a concentration-dependent way. Moreover, ATB stimulated ROS production in MFC cells and inhibited the tumor growth in the MFC-sourced subcutaneous tumor model while not significantly reducing the weight of mice. The pharmacological results suggested that the newly discovered ATB may be a promising anti-tumor lead compound. KEY POINTS: • Eight structurally diverse prenylated indole alkaloids including a new aspertaichamide B (ATB) were isolated from the fungus Aspergillus japonicus TE-739D. • The structure of ATB was elucidated by HRESIMS, NMR, NMR calculations with DP4 + probability analysis, and ECD calculations. • ATB inhibited cell proliferation, promoted apoptosis, and increased ROS production in gastric cancer cells, and exhibited inhibitory effects on tumor growth in vivo., (© 2024. The Author(s).)

Objective: The aim of this study is to evaluate the significance of combined detection of Septin9 and syndecan-2 (SDC2) methylation markers and serum tumor markers for the early diagnosis of colorectal cancer., Methods: A total of 116 patients diagnosed with colorectal cancer between December 2022 and February 2024 were designated as the colorectal cancer group. Additionally, 31 patients with colorectal adenoma were assigned to the adenoma group, while 44 individuals undergoing routine physical examinations were included in the control group. Concentrations of Septin9, SDC2, fecal occult blood (FOB), and four tumor markers-carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), and carbohydrate antigen 724 (CA724)-were measured. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves for Septin9, SDC2, the four tumor markers, FOB, the combination of Septin9 and SDC2, and the combined use of all seven indicators (CEA, CA19-9, CA125, CA72-4, FOB, Septin9, and SDC2)., Results: The colorectal cancer group exhibited the highest positive rates for Septin9, SDC2, the four tumor markers, the combined detection of Septin9 and SDC2, and the combined detection of all seven indicators, compared to both the adenoma and control groups (P < 0.05). The adenoma group also showed higher positive rates than the control group (P < 0.05). For patients with stage I-III colorectal cancer, the positive rates for the combined detection of Septin9 and SDC2 were 81.3%, 78.9%, and 90.2%, respectively, surpassing those for the combined detection of the four tumor markers (43.8%, 55.3%, and 61.0%). Additionally, the positive rates for the two-gene combination in stage III colorectal cancer were higher than those for FOB (P < 0.05). The sensitivity and area under the curve (AUC) for SDC2 were 73.3% and 0.855, respectively, exceeding the sensitivity and AUC for the combined four tumor markers, which were 60.3% and 0.734 (P < 0.05). The combined detection of the two methylated genes demonstrated a sensitivity of 86.2% and an AUC of 0.908, outperforming both FOB and the combined detection of the four tumor markers (P < 0.05)., Conclusion: The detection of SDC2 exhibits high sensitivity for colorectal cancer, and when combined with Septin9, it significantly enhances the diagnostic accuracy for early-stage colorectal cancer, offering substantial clinical value., (© 2024. The Author(s).)

MT-1207 (MT) as a new antihypertensive drug is under clinical trial. However, its hypotensive mechanism has not been experimentally explored, and it is unknown whether MT can be used for bilateral renal artery stenosis hypertension. Using two-kidney two-clip (2K2C) to mimic bilateral renal artery stenosis in rats, a stroke-prone renovascular hypertension model, the present study further verified its antihypertensive effect, cardiovascular and renal protection, mortality reduction and lifespan prolongation, as well as demonstrated its two novel pharmacological effects for uric acid-lowering and cognition-improving. Notably, MT did not aggravate renal dysfunction; instead, it had beneficial effects on reducing serum uric acid level and maintaining serum K + at a relatively stable level in 2K2C rats. In contrast, angiotensin receptor blocker losartan aggravated renal dysfunction in 2K2C rats. Mechanistically, MT hypotensive effect was dependent on its blockade of α 1 and 5-HT 2 receptors, since MT pretreatment abolished these receptor agonists-induced blood pressure elevations in vivo. Further evidence showed MT bound to and interacted with these receptor subtypes including α 1A , α 1B , α 1D , 5-HT 2A , 5-HT 2B , and 5-HT 2C receptors known for control of blood pressure. In conclusion, MT may be used for treatment of bilateral renal artery stenosis hypertension, different from losartan that is prohibited for treatment of bilateral renal artery stenosis hypertension. Targets validation of MT hypotensive mechanism and beneficial effects of MT on uric acid and cognitive function provide new insights for this novel multitarget drug, deserving clinical trial attention., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Study Objective: We compared the analgesic effects of erector spinae plane block versus quadratus lumborum block following laparoscopic nephrectomy., Design: A randomized controlled trial., Setting: A tertiary hospital in Beijing, China., Patients: Patients scheduled for elective laparoscopic nephrectomy., Interventions: A total of 110 patients were enrolled and randomized to receive either erector spinae plane block (n = 55) or quadratus lumborum block (n = 55) under ultrasound guidance. Patient-controlled sufentanil analgesia was provided after surgery., Measurements: Our primary outcome was cumulative opioid consumption within 24 h after surgery. Secondary outcomes included postoperative pain intensity, subjective sleep quality, and quality of recovery., Main Results: All 110 patients (mean 53 years, 57.3% female) were included in the intention-to-treat analysis. Cumulative sufentanil equivalent within 24 h was lower in patients given erector spinae plane block (median 13 μg, interquartile range 4 to 33) than in those given quadratus lumborum block (median 25 μg, interquartile range 13 to 39; median difference - 8 μg, 95% CI -15 to 0, P = 0.041). Pain intensity (0-10 range where 0 = no pain and 10 = the worst pain) at 2, 6, 12, and 24 h after surgery was lower with erector spinae plane block (at rest: median differences -1 point, all P ≤ 0.009; with movement: median differences -2 to -1 points, all P < 0.001). Subjective sleep quality on the night of surgery (the Richards-Campbell Sleep Questionnaire: 0-100 range, higher score better; median difference 12, 95% CI 2 to 23, P = 0.018) and quality of recovery at 24 h (the Quality of Recovery-15: 0-150 range, higher score better; median difference 8, 95% CI 2 to 15, P = 0.012) were better with erector spinae plane block. No procedure-related adverse events occurred., Conclusions: Compared with quadratus lumborum block, erector spinae plane block provided better analgesia as manifested by lower opioid consumption and pain intensity for up to 24 h after laparoscopic nephrectomy., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in this work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to examine demographic and surgical factors that influence patient-reported knee function in patients who undergo anterior crucial ligament reconstruction (ACLR) with concurrent bucket-handle meniscal tear (BHMT) procedures. We hypothesized that repair of BHMT in the setting of concomitant ACLR and shorter time from injury to surgery would lead to improved patient-reported outcomes., Methods: Forty-one patients (mean age: 28.0 ± 9.8 years, 72% male) with BHMT at the time of ACLR completed the International Knee Documentation Committee Subjective Knee Form (IKDC-SKF) via online survey at an average of 15.2 months postop. Patient demographics and surgical characteristics, including time from injury to surgery, were compared between repair ( n  = 22) and meniscectomy ( n  = 19) groups using one-way analysis of variances; distributions of sex, graft source, BHMT compartment and zone were compared between groups using χ 2 tests. The association between IKDC-SKF score, demographics and surgical characteristics was evaluated using multivariable linear regression. A priori alpha level was p  < 0.05., Results: Meniscal repair and meniscectomy groups differed based on graft source and BHMT zone but not IKDC-SKF score ( p  = 0.085). Patients undergoing ACLR with autograft ( p  = 0.003) and with red-red zone BHMT ( p  < 0.001) more often underwent meniscal repair. The regression model demonstrated longer time from injury to surgery ( p  = 0.049), red-red tear zone ( p  = 0.04) and meniscectomy ( p  = 0.008); these were predictive of poorer IKDC-SKF scores., Conclusion: BHMT repair was more likely performed in ACL autograft and on red-red zone tears. Longer time from injury to surgery is an indicator of poorer IKDC-SKF score, as this may increase the risk of concomitant pathologies. White-white zone BHMTs are associated with better IKDC-SKF scores than red-red zone BHMTs, which may be due to the smaller volume of tissue removed during meniscectomy of white-white zone tears and the avoidance of iatrogenic complications of meniscal repair., Level of Evidence: Level III, therapeutic study., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Plants synthesise a vast array of volatile organic compounds (VOCs), which serve as chemical defence and communication agents in their interactions with insect herbivores. Although nitrogen (N) is a critical resource in the production of plant metabolites, its regulatory effects on defensive VOCs remain largely unknown. Here, we investigated the effect of N content in tomato (Solanum lycopersicum) on the tobacco cutworm (Spodoptera litura), a notorious agricultural pest, using biochemical and molecular experiments in combination with insect behavioural and performance analyses. We observed that on tomato leaves with different N contents, S. litura showed distinct feeding preference and growth and developmental performance. Particularly, metabolomics profiling revealed that limited N availability conferred resistance upon tomato plants to S. litura is likely associated with the biosynthesis and emission of the volatile metabolite α-humulene as a repellent. Moreover, exogenous application of α-humulene on tomato leaves elicited a significant repellent response against herbivores. Thus, our findings unravel the key factors involved in N-mediated plant defence against insect herbivores and pave the way for innovation of N management to improve the plant defence responses to facilitate pest control strategies within agroecosystems., (© 2024 John Wiley & Sons Ltd.)

Background and Aim: The purpose of the current study was to investigate the predictive value of hepatitis B core-related antigen (HBcrAg) on the occurrence and recurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB)., Methods: We searched PubMed, Embase, Scopus, and Web of Science from database inception to April 6, 2023. Pooled hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was calculated for the occurrence and recurrence of HCC., Results: Of the 464 articles considered, 18 articles recruiting 10 320 patients were included. The pooled results showed that high serum HBcrAg level was an independent risk factor for the occurrence of HCC in CHB patients (adjusted HR = 3.12, 95% CI: 2.40-4.06, P < 0.001, I 2  = 43.2%, P = 0.043; OR = 5.65, 95% CI: 3.44-5.82, P < 0.001, I 2  = 0.00%, P = 0.42). Further subgroup analysis demonstrated that the predictive ability of HBcrAg for the occurrence of HCC is not influenced by the hepatitis B e antigen (HBeAg) status or the use of nucleoside/nucleotide analogs (NAs). In addition, our meta-analysis also suggests that HBcrAg is a predictor of HCC recurrence (adjusted HR = 1.71, 95% CI: 1.26-2.32, P < 0.001, I 2  = 7.89%, P = 0.031)., Conclusions: For patients with CHB, serum HBcrAg may be a potential predictive factor for the occurrence of HCC, regardless of HBeAg status or NA treatment. It may also serve as a novel prognostic biomarker for the recurrence of HCC. More studies are needed to confirm our conclusions., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Presented herein is the exploration of a novel non-covalent anion-carbonyl (X - ···C═O) interaction using aromatic imides as receptors and halides as lone pair donors. Combined theoretical calculations and experimental methods including 13 C NMR, IR, and crystallographic analyses were performed to provide the physical origin and experimental evidence of anion-carbonyl interactions. The EDA analysis (energy decomposition analysis) based on DFT calculation indicates that electrostatic terms are the dominant contributions for the binding energy while electron delocalization also significantly contributes alongside the electrostatic attraction. Orbital interaction (n → π*) involving the delocalization of halide lone pairs on the carbonyl antibonding orbitals was visualized with NBO (Natural Bond Orbital) analysis. 13 C NMR and IR spectra demonstrated upfield chemical shifts and red-shift frequency of hosts upon the addition of halides, reflecting the effect of orbital overlap between the halide lone pairs and π* of carbonyl (n → π* contribution). The anion-carbonyl interactions were directly revealed by X-ray structural analysis of anion and benzene triimide complexes.

The selectivity of multicarbon products in the CO 2 reduction reaction (CO 2 RR) depends on the spin alignment of neighboring active sites, which requires a spin catalyst that facilitates electron transfer with antiparallel spins for enhanced C-C coupling. Here, we design a radical-contained spin catalyst (TEMPOL@HKUST-1) to enhance CO 2 -to-ethylene conversion, in which spin-disordered (SDO) and spin-ordered (SO) phases co-exist to construct an asymmetric spin configuration of neighboring active sites. The replacement of axially coordinated H 2 O molecules with TEMPOL radicals introduces spin-spin interactions among the Cu(II) centers to form localized SO phases within the original H 2 O-mediated SDO phases. Therefore, TEMPOL@HKUST-1 derived catalyst exhibited an approximately two-fold enhancement in ethylene selectivity during the CO 2 RR at -1.8 V versus Ag/AgCl compared to pristine HKUST-1. In situ ATR-SEIRAS spectra indicate that the spin configuration at asymmetric SO/SDO sites significantly reduces the kinetic barrier for *CO intermediate dimerization toward the ethylene product. The performance of the spin catalyst is further improved by spin alignment under a magnetic field, resulting in a maximum ethylene selectivity of more than 50 %. The exploration of the spin-polarized kinetics of the CO 2 RR provides a promising path for the development of novel spin electrocatalysts with superior performance., (© 2024 Wiley-VCH GmbH.)

The role of endothelial cells in acute lung injury (ALI) has been widely elaborated, but little is known about the role of different subtypes of endothelial cells in ALI. ALI models were established by lipopolysaccharide. Single-cell RNA sequencing was used to identify differential molecules in endothelial subtypes and the heterogeneity of lung immune cells. Specific antibodies were used to block insulin-like growth factor binding protein 7 (IGFBP7), and AAV shIGP7 was used to specifically knock down IGFBP7. Here, we found that IGFBP7 was the most differentially expressed molecule in diverse subsets of endothelial cells and that IGFBP7 was strongly associated with inflammatory responses. Elevated IGFBP7 significantly exacerbated barrier dysfunction in ALI, whereas blockade of IGFBP7 partially reversed barrier damage. General capillary cells are the primary source of elevated serum IGFBP7 after ALI. Using single-cell RNA sequencing, we identified significantly increased Clec4n hi neutrophils in mice with ALI, whereas IGFBP7 knockdown significantly reduced infiltration of Clec4n hi cells and mitigated barrier dysfunction in ALI. In addition, we found that IGFBP7 activated the NF-κB signaling axis by promoting phosphorylation and ubiquitination degradation of F-box/WD repeat-containing protein 2 (FBXW2), thereby exacerbating barrier dysfunction in ALI. Taken together, our data indicate that blockade of serum IGFBP7 or IGFBP7 depletion in general capillary cells reversed barrier damage in ALI. Therefore, targeting IGFBP7 depletion could be a novel strategy for treating ALI.

To reduce the risk of atherosclerotic disease, it is necessary to not only diagnose the presence of atherosclerotic plaques but also assess the vulnerability risk of plaques. Accurate detection of the reactive oxygen species (ROS) level at plaque sites represents a reliable way to assess the plaque vulnerability. Herein, through a simple one-pot reaction, two near-infrared (NIR) fluorescent dyes, one is ROS responsive and the other is inert to ROS, are coassembled in an amphiphilic amino acid-assembled nanoparticle. In the prepared NIR fluorescent amino acid nanoparticle (named FANP), the fluorescent properties and ROS-responsive behaviors of the two fluorescent dyes are well maintained. Surface camouflage through red blood cell membrane (RBCM) encapsulation endows the finally obtained FANP@RBCM nanoprobe with not only further reduced cytotoxicity and improved biocompatibility but also increased immune escape capability, prolonged blood circulation time, and thus enhanced accumulation at atherosclerotic plaque sites. In vitro and in vivo experiments demonstrate that FANP@RBCM not only works well in probing the occurrence of atherosclerotic plaques but also enables plaque vulnerability assessment through the accurate detection of the ROS level at plaque sites in a reliable ratiometric mode, thereby holding great promise as a versatile tool for the diagnosis and risk assessment of atherosclerotic disease.

Background: Lower socioeconomic status and public insurance lead to a longer delay to surgery and a higher likelihood of concomitant pathology before undergoing anterior cruciate ligament reconstruction (ACLR). However, few studies have examined the influence of community deprivation on ACLR timing and outcomes., Purpose/hypothesis: The primary aim of this study was to define the effect of the area deprivation index (ADI) and insurance classification on access to orthopaedic care after an ACL rupture, and the secondary aim was to determine whether these variables were associated with a second ACL injury after primary ACLR. It was hypothesized that patients with a greater national ADI percentile and Medicaid insurance would experience longer delays to care and an increased risk of reinjury after ACLR., Study Design: Cohort study; Level of evidence, 3., Methods: A retrospective study was performed to evaluate patients undergoing primary ACLR between 2016 and 2019. The national ADI percentile was obtained utilizing the Neighborhood Atlas website. The relationship between national ADI percentile and care characteristics (eg, time to specialized care) was investigated using the Spearman rho correlation coefficient ( r ). The association between patient and care characteristics and second ACL injury after the index procedure (ie, graft rerupture or contralateral ACL rupture) was investigated using binary logistic regression., Results: A total of 197 patients met the inclusion criteria. Longer times from injury to surgery ( r = 0.238; P < .001) and from specialized care to surgery ( r = 0.217; P = .002) were associated with a greater national ADI percentile. The second injury group reported significantly greater national ADI ( P = .026) and included a greater percentage of patients with Medicaid insurance (31.3%) compared with the no second injury group. Patients experienced 5.1% greater odds of a second ACL injury for each additional month between evaluation and surgery., Conclusion: Greater national ADI percentile and Medicaid insurance status were associated with adverse ACLR timing and outcomes. Patients with a greater national ADI percentile took significantly longer to obtain surgery after ACL injury. Those who sustained a second ACL injury after ACLR had an overall higher mean national ADI percentile and included a greater proportion of patients with Medicaid compared with those who did not sustain a second ACL injury. Future studies should critically investigate the underlying factors of these associations to reach equity in orthopaedic care., Competing Interests: The authors declared that they have the following conflicts of interest: A.J.C. has received education payments from Arthrex, Medwest Associates, Mid-Atlantic Surgical Systems LLC, Smith+Nephew, and Supreme Orthopedic Systems LLC; hospitality payments from Stryker; and a grant from Arthrex. B.M.B. has received education payments from Conetic Solutions, Arthrex, Smith+Nephew, and Medwest Associates; hospitality payments from Stryker, Smith+Nephew, Conetic Solutions, and Medical Device Business Services; honoraria from Encore Medical LP; and a grant from Arthrex. C.M.C. has received education payments from Liberty Surgical and hospitality payments from Medical Device Business Services. E.S.C. has received consulting fees from Avanos Medical; education payments from Arthrex and Supreme Orthopedic Systems LLC; and hospitality payments from Arthrex. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Ethical approval for this study was obtained from the Western Institutional Review Board-Copernicus Group (ref No. 20216925)., (© The Author(s) 2024.)

The landscape of current tumor treatment has been revolutionized by the advent of immunotherapy based on PD-1/PD-L1 inhibitors. Leveraging its capacity to mobilize systemic antitumor immunity, which is primarily mediated by T cells, there is growing exploration and expansion of its potential value in various stages of clinical tumor treatment. Neoadjuvant immunotherapy induces a robust immune response against tumors prior to surgery, effectively facilitating tumor volume reduction, early eradication or suppression of tumor cell activity, and control of potential metastatic spread, to improve curative surgical resection rates, and prevent tumor recurrence. This review delineates the theoretical basis of neoadjuvant immunotherapy from preclinical research evidence, discusses specific challenges in clinical application, and provides a comprehensive overview of clinical research progress in neoadjuvant immunotherapy for gastrointestinal tumors. These findings suggest that neoadjuvant immunotherapy has the potential to ameliorate immunosuppressive states and enhance cytotoxic T cell function while preserving lymphatic drainage in the preoperative period. However, further investigations are needed on specific treatment regimens, suitable patient populations, and measurable endpoints. Despite numerous studies demonstrating the promising efficacy and manageable adverse events of neoadjuvant immunotherapy in gastrointestinal tumors, the availability of high-quality randomized controlled trials is limited, which highlights the necessity for further research., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To assess the compliance with a lung protective ventilation strategy and to evaluate the relationship with prognosis in patients with acute respiratory distress syndrome (ARDS). Methods: In the prospective multicenter cohort study (CHARDS), patients with ARDS undergoing invasive mechanical ventilation were enrolled to collect essential information, mechanical ventilation data, and prognostic data. Compliance was operationally defined as tidal volume ≤7 ml/kg predicted body weight (PBW) or plateau pressure ≤30 cmH 2 O or driving pressure≤15 cmH 2 O. Tidal volume data collected 7 days prior to ventilation after ARDS diagnosis were categorized into four groups: standard group (Group A, 100% compliance), non-standard group (Group B, 50%-99% compliance, Group C,1%-49% compliance,and Group D,totally non-compliant). Plateau pressure and drive pressure measurements were recorded on the first day. Stepwise regression, specifically Logistics regression, was used to identify the factors influencing ICU survival. Results: A total of 449 ARDS patients with invasive mechanical ventilation were included; the proportion of mild, moderate, and severe patients was 71 (15.8%), 198 (44.1%) and 180 (40.1%), respectively. During the first 7 days, a total of 2880 tidal volume measurements were recorded with an average tidal volume of (6.89±1.93) ml/kg PBW. Of these measurements, 53.2% were found to be≤7 ml/kg PBW. The rates of compliance with lung protective mechanical ventilation were 29.8% (134/449), 24.5% (110/449), 23.6% (106/449), and 22% (99/449) in groups A, B, C, and D, respectively. In the standard group, the tidal volume for mild ARDS patients was 18.3%(13/71), while it was 81.7%(58/71)in the non-standard group. Similarly, in patients with moderate ARDS, the tidal volume was 25.8% (51/198) in the standard group, while it was 74.2% (147/198) in the non-standard group. Finally, in patients with severe ARDS, the tidal volume was 38.9% (70/180) in the standard group, while it was 61.1% (110/180) in the non-standard group. Notably, the compliance rate was higher in patients with moderate and severe ARDS in group A compared to patients with mild and moderate ARDS (18.3% vs. 25.8% vs. 38.9%, χ 2 =13.124, P =0.001). Plateau pressure was recorded in 221 patients, 95.9% (212/221) patients with plateau pressure≤30 cmH 2 O, and driving pressure was recorded in 207 patients, 77.8% (161/207) patients with a driving pressure ≤15 cmH 2 O.During the first 7 days, the mortality rate in the intensive care unit (ICU) was lower in the tidal volume standard group compared to the non-standard group (34.6% vs. 51.3%, χ 2 =10.464, P =0.001). In addition, the in-hospital mortality rate was lower in the standard group compared to the non-standard group (39.8% vs. 57%, χ 2 =11.016, P =0.001).The results of the subgroup analysis showed that the mortality rates of moderate and severe ARDS patients in the standard group were significantly lower than those in the non-standard group, both in the ICU and in the hospital (all P <0.05). However, there was no statistically significant difference in mortality among mild ARDS patients (all P >0.05). Conclusions: There was high compliance with recommended lung protective mechanical ventilation strategies in ARDS patients, with slightly lower compliance in patients with mild ARDS, and high compliance rates for plateau and drive pressures. The tidal volume full compliance group had a lower mortality than the non-compliance group, and showed a similar trend in the moderate-to-severe ARDS subgroup, but there was no significant correlation between compliance and prognosis in patients with mild ARDS subgroup.

Background: The effect of age, sex, and eastern cooperative oncology group performance status (ECOG PS) on the efficacy and safety of immune checkpoint inhibitor (ICI) therapy among hepatocellular carcinoma (HCC) patients remains elusive. Thus, a meta-analysis was conducted to evaluate whether such effects exist., Research Design and Methods: Eligible studies in PubMed, Embase, and Cochrane Library databases were retrieved., Results: One-hundred-and-eleven studies involving 14,768 HCC patients were included. The findings indicated that the ECOG PS didn't have a significant effect on the ORR and PFS in ICI-treated HCC patients (higher ECOG PS vs. lower ECOG PS: ORR: OR  = 0.78, 95%CI = 0.55-1.10; PFS: HR  = 1.15, 95%CI = 0.97-1.35), while those patients with a higher ECOG PS may have a worse OS ( HR  = 1.52, 95% CI = 1.26-1.84). There is no significant evidence of the effect of age (older vs. younger) or sex (males vs. females) on the efficacy of ICI therapy in HCC., Conclusion: ICI therapy in HCC should not be restricted strictly to certain patients in age or sex categories, while HCC patients with higher ECOG PS may require closer medication or follow-up strategy during ICI therapy., Prospero Registration: CRD42024518407.

Incorporation of privileged catalytic scaffolds into a macrocyclic skeleton represents an attractive strategy to furnish supramolecular catalysis systems with enzyme-mimetic cavity and multi-site cooperation. Herein we reported the synthesis, structure, binding properties and catalytic application of a series of chiral bis-phosphate macrocycles toward the challenging asymmetric electrophilic fluorination. With a large, integrated chiral cavity and two cooperative phosphate sites, these macrocycles exhibited good inclusion toward 1,4-diazabicyclo[2.2.2]octane (DABCO) dicationic ammoniums through complementary ion-pair and C-H⋅⋅⋅O interactions, as confirmed by crystallographic and solution binding studies. In fluorocyclization of tryptamines with Selectfluor reagent which has a similar DABCO-based dicationic structure, only 2 mol% macrocycle catalyst afforded the desired pyrroloindoline products in moderate yields and up to 91 % ee. For comparison, the acyclic mono-phosphate analogue gave obviously lower reactivity and enantioselectivity (<20 % ee), suggesting a remarkable macrocyclic effect. The high catalytic efficiency and superior stereocontrol were ascribed to the tight ion-pair binding and cavity-directed noncovalent interaction cooperation., (© 2024 Wiley-VCH GmbH.)

Objective: Ciprofol (also known as cipepofol and HSK3486), is a compound similar to propofol in chemical structure and hypnotic effect. Herein we evaluated the efficacy and safety of ciprofol for sedation in outpatient gynecological procedures., Methods: This phase III multicenter randomized trial with a non-inferiority design was conducted in nine tertiary hospitals. We enrolled 135 women aged 18-65 years who were scheduled for ambulatory gynecological procedures. Patients were randomly assigned to receive either ciprofol (0.4 mg/kg for induction and 0.2 mg/kg for maintenance) or propofol (2.0 mg/kg for induction and 1.0 mg/kg for maintenance) sedation in a 2:1 ratio. Patients and investigators for data collection and outcome assessment were blinded to study group assignments. The primary outcome was the success rate of sedation, defined as completion of procedure without remedial anesthetics. The non-inferiority margin was set at -8%. Secondary outcomes included time to successful induction, time to full awake, time to meet discharge criteria, and satisfaction with sedation assessed by patients and doctors. We also monitored occurrence of adverse events and injection pain., Results: A total of 135 patients were enrolled; 134 patients (90 patients received ciprofol sedation and 44 patients propofol sedation) were included in final intention-to-treat analysis. The success rates were both 100% in the two groups (rate difference, 0.0%; 95% CI, -4.1 to 8.0%), i.e., ciprofol was non-inferior to propofol. When compared with propofol sedation, patients given ciprofol required more time to reach successful induction (median difference [MD], 2 s; 95% CI, 1 to 7; p < 0.001), and required more time to reach full awake (MD, 2.3 min; 95% CI, 1.4 to 3.1; p < 0.001) and discharge criteria (MD, 2.3 min; 95% CI, 1.5 to 3.2; p < 0.001). Fewer patients in the ciprofol group were dissatisfied with sedation (relative risk, 0.21; 95% CI, 0.06 to 0.77; p = 0.024). Patients given ciprofol sedation had lower incidences of treat-emergent adverse events (34.4% [31/90] vs. 79.5% [35/44]; p < 0.001) and injection pain (6.7% [6/90] vs. 61.4% [27/44]; p < 0.001)., Conclusion: Ciprofol for sedation in ambulatory gynecological procedures was non-inferior to propofol, with less adverse events and injection pain., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04958746., Competing Interests: The authors declare that this study received funding from Haisco Pharmaceutical Group Co., Ltd. The funder had the following involvement in the study: data collection, analysis and draft writing., (Copyright © 2024 Xu, Yang, Zeng, Zou, Ren, Xia, Xie, Yu, Xu, Chen and Wang.)

Sensors designed based on the trans -cleavage activity of CRISPR/Cas12a systems have opened up a new era in the field of biosensing. The current design of CRISPR/Cas12-based sensors in the "on-off-on" mode mainly focuses on programming the activator strand (AS) to indirectly switch the trans -cleavage activity of Cas12a in response to target information. However, this design usually requires the help of additional auxiliary probes to keep the activator strand in an initially "blocked" state. The length design and dosage of the auxiliary probe need to be strictly optimized to ensure the lowest background and the best signal-to-noise ratio. This will inevitably increase the experiment complexity. To solve this problem, we propose using AS after the "RESET" effect to directly regulate the Cas12a enzymatic activity. Initially, the activator strand was rationally designed to be embedded in a hairpin structure to deprive its ability to activate the CRISPR/Cas12a system. When the target is present, target-mediated strand displacement causes the conformation change in the AS, the hairpin structure is opened, and the CRISPR/Cas12a system is reactivated; the switchable structure of AS can be used to regulate the degree of activation of Cas12a according to the target concentration. Due to the advantages of low background and stability, the CRISPR/Cas12a-based strategy can not only image endogenous biomarkers (miR-21) in living cells but also enable long-term and accurate imaging analysis of the process of exogenous virus invasion of cells. Release and replication of virus genome in host cells are indispensable hallmark events of cell infection by virus; sensitive monitoring of them is of great significance to revealing virus infection mechanism and defending against viral diseases.

Background: Regular physical activity during childhood and adolescence is beneficial to bone development, as evidenced by the ability to increase bone density and peak bone mass by promoting bone formation., Aim: To investigate the effects of exercise on bone formation in growing mice and to investigate the underlying mechanisms., Methods: 20 growing mice were randomly divided into two groups: Con group (control group, n = 10) and Ex group (treadmill exercise group, n = 10). Hematoxylin-eosin staining, immunohistochemistry, and micro-CT scanning were used to assess the bone formation-related indexes of the mouse femur. Bioinformatics analysis was used to find potential miRNAs targets of long non-coding RNA H19 (lncRNA H19). RT-qPCR and Western Blot were used to confirm potential miRNA target genes of lncRNA H19 and the role of lncRNA H19 in promoting osteogenic differentiation., Results: Compared with the Con group, the expression of bone morphogenetic protein 2 was also significantly increased. The micro-CT results showed that 8 wk moderate-intensity treadmill exercise significantly increased bone mineral density, bone volume fraction, and the number of trabeculae, and decreased trabecular segregation in the femur of mice. Inhibition of lncRNA H19 significantly upregulated the expression of miR-149 and suppressed the expression of markers of osteogenic differentiation. In addition, knockdown of lncRNA H19 significantly downregulated the expression of autophagy markers, which is consistent with the results of autophagy-related protein changes detected in mouse femurs by immunofluorescence., Conclusion: Appropriate treadmill exercise can effectively stimulate bone formation and promote the increase of bone density and bone volume in growing mice, thus enhancing the peak bone mass of mice. The lncRNA H19/miR-149 axis plays an important regulatory role in osteogenic differentiation., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

ClC is the main family of natural chloride channel proteins that transport Cl - across the cell membrane with high selectivity. The chloride transport and selectivity are determined by the hourglass-shaped pore and the filter located in the central and narrow region of the pore. Artificial unimolecular channel that mimics both the shape and function of the ClC selective pore is attractive, because it could provide simple molecular model to probe the intriguing mechanism and structure-function relevance of ClC. Here we elaborated upon the concept of molecular hourglass plus anion-π interactions for this purpose. The concept was validated by experimental results of molecular hourglasses using shape-persistent 1,3-alternate tetraoxacalix[2]arene[2]triazine as the central macrocyclic skeleton to control the conductance and selectivity, and anion-π interactions as the driving force to facilitate the chloride dehydration and movement along the channel., (© 2024 Wiley‐VCH GmbH.)

Stellera chamaejasme (S. chamaejasme) is an important medicinal plant with heat-clearing, detoxifying, swelling and anti-inflammatory effects. At the same time, it is also one of the iconic plants of natural grassland degradation in northwest China, playing a key role in the invasion process. Plant endophytes live in healthy plant tissues and can synthesize substances needed for plant growth, induce disease resistance in host plants, and enhance plant resistance to environmental stress. Therefore, studying the root endophytes of S. chamaejasme is of great significance for mining beneficial microbial resources and biological prevention and control of S. chamaejasme. This study used Illumina MiSeq high-throughput sequencing technology to analyze the composition and diversity of endophytes in the roots of S. chamaejasme in different alpine grasslands (BGC, NMC and XGYZ) in Tibet. Research results show that the main phylum of endophytic fungi in the roots of S. chamaejasme in different regions is Ascomycota, and the main phyla of endophytic bacteria are Actinobacteria, Proteobacteria and Firmicutes (Bacteroidota). Overall, the endophyte diversity of the NMC samples was significantly higher than that of the other two sample sites. Principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) results showed significant differences in the composition of endophytic bacterial and fungal communities among BGC, NMC and XGYZ samples. Co-occurrence network analysis of endophytes showed that there were positive correlations between fungi and some negative correlations between bacteria, and the co-occurrence network of bacteria was more complex than that of fungi. In short, this study provides a vital reference for further exploring and utilizing the endophyte resources of S. chamaejasme and an in-depth understanding of the ecological functions of S. chamaejasme endophytes., (© 2024. The Author(s).)

Objective: To determine whether a single low dose of esketamine administered after childbirth reduces postpartum depression in mothers with prenatal depression., Design: Randomised, double blind, placebo controlled trial with two parallel arms., Setting: Five tertiary care hospitals in China, 19 June 2020 to 3 August 2022., Participants: 364 mothers aged ≥18 years who had at least mild prenatal depression as indicated by Edinburgh postnatal depression scale scores of ≥10 (range 0-30, with higher scores indicating worse depression) and who were admitted to hospital for delivery., Interventions: Participants were randomly assigned 1:1 to receive either 0.2 mg/kg esketamine or placebo infused intravenously over 40 minutes after childbirth once the umbilical cord had been clamped., Main Outcome Measures: The primary outcome was prevalence of a major depressive episode at 42 days post partum, diagnosed using the mini-international neuropsychiatric interview. Secondary outcomes included the Edinburgh postnatal depression scale score at seven and 42 days post partum and the 17 item Hamilton depression rating scale score at 42 days post partum (range 0-52, with higher scores indicating worse depression). Adverse events were monitored until 24 hours after childbirth., Results: A total of 364 mothers (mean age 31.8 (standard deviation 4.1) years) were enrolled and randomised. At 42 days post partum, a major depressive episode was observed in 6.7% (12/180) of participants in the esketamine group compared with 25.4% (46/181) in the placebo group (relative risk 0.26, 95% confidence interval (CI) 0.14 to 0.48; P<0.001). Edinburgh postnatal depression scale scores were lower in the esketamine group at seven days (median difference -3, 95% CI -4 to -2; P<0.001) and 42 days (-3, -4 to -2; P<0.001). Hamilton depression rating scale scores at 42 days post partum were also lower in the esketamine group (-4, -6 to -3; P<0.001). The overall incidence of neuropsychiatric adverse events was higher in the esketamine group (45.1% (82/182) v 22.0% (40/182); P<0.001); however, symptoms lasted less than a day and none required drug treatment., Conclusions: For mothers with prenatal depression, a single low dose of esketamine after childbirth decreases major depressive episodes at 42 days post partum by about three quarters. Neuropsychiatric symptoms were more frequent but transient and did not require drug intervention., Trial Registration: ClinicalTrials.gov NCT04414943., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the National Natural Science Foundation of China, National High Level Hospital Clinical Research Funding, Peking University First Hospital, and Zhejiang University; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Optimization of medical factors including diabetes and obesity is a cornerstone in the prevention of prosthetic joint infection (PJI). Dyslipidaemia is another component of metabolic syndrome which has not been thoroughly investigated as an individual, modifiable risk factor. This study examined the association of dyslipidaemia with PJI caused by the lipophilic microbe Cutibacterium acnes (C. acnes)., Methods: A retrospective chart review examined patients with positive C. acnes culture at hip or knee arthroplasty explantation. A control group with methicillin-sensitive Staphylococcus aureus (MSSA) positive cultures at explantation was matched for age, sex, and surgical site, as well as a second control group with no infection. A total of 80 patients were included, 16 with C. acnes, 32 with MSSA, and 32 with no infection. All patients had a lipid panel performed within one year of surgery. Lipid values and categories were compared using multinomial logistic regressions., Results: High or borderline triglycerides (TG) (relative risk ratio (RRR) = 0.13; P = 0.013) and low high-density lipoprotein (HDL) (RRR = 0.13; P = 0.025) were significantly associated with C. acnes PJI compared to MSSA-PJI. High or borderline TG (RRR = 0.21; P = 0.041) and low HDL (RRR = 0.17; P = 0.043) were also associated with a greater probability of C. acnes infection compared to no infection., Conclusions: The presence of elevated TG and low HDL were both associated at a statistically significant level with C. acnes hip or knee PJI compared to controls with either MSSA PJI or no infection. This may represent a specific risk factor for C. acnes PJI that is modifiable., (© 2023. The Author(s) under exclusive licence to SICOT aisbl.)

Chronic kidney disease (CKD) is a global health burden, with ineffective therapies leading to increasing morbidity and mortality. Renal interstitial fibrosis is a common pathway in advanced CKD, resulting in kidney function and structure deterioration. In this study, we investigate the role of FTO-mediated N6-methyladenosine (m6A) and its downstream targets in the pathogenesis of renal fibrosis. M6A modification, a prevalent mRNA internal modification, has been implicated in various organ fibrosis processes. We use a mouse model of unilateral ureteral obstruction (UUO) as an in vivo model and treated tubular epithelial cells (TECs) with transforming growth factor (TGF)-β1 as in vitro models. Our findings revealed increased FTO expression in UUO mouse model and TGF-β1-treated TECs. By modulating FTO expression through FTO heterozygous mutation mice (FTO +/- ) in vivo and small interfering RNA (siRNA) in vitro, we observed attenuation of UUO and TGF-β1-induced epithelial-mesenchymal transition (EMT), as evidenced by decreased fibronectin and N-cadherin accumulation and increased E-cadherin levels. Silencing FTO significantly improved UUO and TGF-β1-induced inflammation, apoptosis, and inhibition of autophagy. Further transcriptomic assays identified RUNX1 as a downstream candidate target of FTO. Inhibiting FTO was shown to counteract UUO/TGF-β1-induced RUNX1 elevation in vivo and in vitro. We demonstrated that FTO signaling contributes to the elevation of RUNX1 by demethylating RUNX1 mRNA and improving its stability. Finally, we revealed that the PI3K/AKT pathway may be activated downstream of the FTO/RUNX1 axis in the pathogenesis of renal fibrosis. In conclusion, identifying small-molecule compounds that target this axis could offer promising therapeutic strategies for treating renal fibrosis., (© 2024 Federation of American Societies for Experimental Biology.)

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines., Competing Interests: Conflict of interest: W-J. Guan reports consulting fees from Joincare Pharmaceutical Co. Ltd., lecture fees from Joincare Pharmaceutical Co. Ltd., support for travel to attend domestic meetings from Joincare Pharmaceutical Co. Ltd., and is an associate editor of this journal. Conflict of interest: S.H. Chotirmall reports grants paid to his institution from the Singapore Ministry of Education, National Medical Research Council Singapore, consulting fees from CSL Behring, Pneumagen Ltd, Boehringer Ingelheim and Pneumagen Ltd, lecture fees from AstraZeneca and Chiesi, and participation in Data Safety and Monitoring Committees for Inovio Pharmaceuticals and Imam Abdulrahman Bin Faisal University. Conflict of interest: J.D. Chalmers reports grants from GSK, Boehringer Ingelheim, Genentech, Insmed, Grifols, Novartis, Gilead and AstraZeneca, consulting fees from AstraZeneca, Grifols, Genentech, GSK, Chiesi, Zambon, Trudell and Pfizer, and is an associate editor of this journal. Conflict of interest: J.F. Xu reports consulting fees from AstraZeneca and Boehringer Ingelheim. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

Background: Acute respiratory distress syndrome (ARDS) is a severe respiratory condition characterized by a high mortality rate, the management of which relies on supportive care and a profound understanding of its pathophysiology. Heparin, with its anticoagulant and potential anti-inflammatory properties, offers a new therapeutic opportunity for the treatment of ARDS., Methods: In this retrospective cohort study, we examined the MIMIC-IV database for ARDS patients who received prophylactic heparin within the first 72 h of ICU admission. Employing propensity score matching and inverse probability weighting (IPW) analysis, we evaluated the impact of early heparin use on patient outcomes, focusing on mortality rates., Results: Patients who received prophylactic heparin had a significantly lower in-hospital mortality rate compared to those who did not (13.55% vs 17.93%, HR = 0.71, 95% CI: 0.54-0.93, P = 0.012). This result remained significant after propensity score matching (12.75% vs 17.93%, HR = 0.65, 95% CI 0.47-0.90, P = 0.010). Analysis using five different statistical models indicated that early use of heparin significantly reduced the in-hospital mortality rate, with HR = 0.669 (95% CI 0.487-0.919, P = 0.013) in the doubly robust model without balanced covariates; HR = 0.705 (95% CI 0.515-0.965, P = 0.029) with all covariates considered; HR = 0.660 (95% CI 0.491-0.888, P = 0.006) in the propensity score (IPW) model; HR = 0.650 (95% CI 0.470-0.900, P = 0.010) in the propensity score matching model; and HR = 0.706 (95% CI 0.536-0.930, P = 0.013) in the multivariate Cox regression model. Secondary outcomes indicated that heparin use was also associated with reduced mortality rates at 60 days, and 90 days., Conclusion: This research highlights that early prophylactic administration of heparin may substantially lower mortality in ARDS patients. These findings underscore the potential of heparin as a key component in the management of ARDS, offering a new perspective and novel strategies for clinical treatment., (© 2024. The Author(s).)