Oxygen-bridging Fe, Co dual-metal dimers boost reversible oxygen electrocatalysis for rechargeable Zn-air batteries.

Rechargeable zinc-air batteries (ZABs) are regarded as a remarkably promising alternative to current lithium-ion batteries, addressing the requirements for large-scale high-energy storage. Nevertheless, the sluggish kinetics involving oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) hamper the widespread application of ZABs, necessitating the development of high-efficiency and durable bifunctional electrocatalysts. Here, we report oxygen atom-bridged Fe, Co dual-metal dimers (FeOCo-SAD), in which the active site Fe-O-Co-N6 moiety boosts exceptional reversible activity toward ORR and OER in alkaline electrolytes. Specifically, FeOCo-SAD achieves a half-wave potential (E1/2) of 0.87 V for ORR and an overpotential of 310 mV at a current density of 10 mA cm-2 for OER, with a potential gap (ΔE) of only 0.67 V. Meanwhile, FeOCo-SAD manifests high performance with a peak power density of 241.24 mW cm-2 in realistic rechargeable ZABs. Theoretical calculations demonstrate that the introduction of an oxygen bridge in the Fe, Co dimer induced charge spatial redistribution around Fe and Co atoms. This enhances the activation of oxygen and optimizes the adsorption/desorption dynamics of reaction intermediates. Consequently, energy barriers are effectively reduced, leading to a strong promotion of intrinsic activity toward ORR and OER. This work suggests that oxygen-bridging dual-metal dimers offer promising prospects for significantly enhancing the performance of reversible oxygen electrocatalysis and for creating innovative catalysts that exhibit synergistic effects and electronic states.

GPS 6.0: an updated server for prediction of kinase-specific phosphorylation sites in proteins.

Protein phosphorylation, catalyzed by protein kinases (PKs), is one of the most important post-translational modifications (PTMs), and involved in regulating almost all of biological processes. Here, we report an updated server, Group-based Prediction System (GPS) 6.0, for prediction of PK-specific phosphorylation sites (p-sites) in eukaryotes. First, we pre-trained a general model using penalized logistic regression (PLR), deep neural network (DNN), and Light Gradient Boosting Machine (LightGMB) on 490 762 non-redundant p-sites in 71 407 proteins. Then, transfer learning was conducted to obtain 577 PK-specific predictors at the group, family and single PK levels, using a well-curated data set of 30 043 known site-specific kinase-substrate relations in 7041 proteins. Together with the evolutionary information, GPS 6.0 could hierarchically predict PK-specific p-sites for 44046 PKs in 185 species. Besides the basic statistics, we also offered the knowledge from 22 public resources to annotate the prediction results, including the experimental evidence, physical interactions, sequence logos, and p-sites in sequences and 3D structures. The GPS 6.0 server is freely available at https://gps.biocuckoo.cn. We believe that GPS 6.0 could be a highly useful service for further analysis of phosphorylation.

Machine learning-based decision support model for selecting intra-arterial therapies for unresectable hepatocellular carcinoma: A national real-world evidence-based study.

IMPORTANCE: Intra-arterial therapies(IATs) are promising options for unresectable hepatocellular carcinoma(HCC). Stratifying the prognostic risk before administering IAT is important for clinical decision-making and for designing future clinical trials. OBJECTIVE: To develop and validate a machine learning(ML)-based decision support model(MLDSM) for recommending IAT modalities for unresectable HCC. DESIGN, SETTING, AND PARTICIPANTS: Between October 2014 and October 2022, a total of 2,959 patients with HCC who underwent initial IATs were enroled retrospectively from 13 tertiary hospitals. These patients were divided into the training cohort (n = 1700), validation cohort (n = 428), and test cohort (n = 200). MAIN OUTCOMES AND MEASURES: Thirty-two clinical variables were input, and five supervised ML algorithms, including eXtreme Gradient Boosting (XGBoost), Categorical Gradient Boosting (CatBoost), Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LGBM) and Random Forest (RF), were compared using the areas under the receiver operating characteristic curve (AUC) with the DeLong test. RESULTS: A total of 1856 patients were assigned to the IAT alone Group(I-A), and 1103 patients were assigned to the IAT combination Group(I-C). The 12-month death rates were 31.9% (352/1103) in the I-A group and 50.4% (936/1856) in the I-C group. For the test cohort, in the I-C group, the CatBoost model achieved the best discrimination when 30 variables were input, with an AUC of 0.776 (95% confidence intervals [CI], 0.833-0.868). In the I-A group, the LGBM model achieved the best discrimination when 24 variables were input, with an AUC of 0.776 (95% CI, 0.833-0.868). According to the decision trees, BCLC grade, local therapy, and diameter as top three variables were used to guide clinical decisions between IAT modalities. CONCLUSIONS AND RELEVANCE: The MLDSM can accurately stratify prognostic risk for HCC patients who received IATs, thus helping physicians to make decisions about IAT and providing guidance for surveillance strategies in clinical practice.

Prognosis prediction and risk stratification of transarterial chemoembolization or intraarterial chemotherapy for unresectable hepatocellular carcinoma based on machine learning.

OBJECTIVE: To develop and validate a risk scoring scale model (RSSM) for stratifying prognostic risk after intra-arterial therapies (IATs) for hepatocellular carcinoma (HCC). METHODS: Between February 2014 and October 2022, 2338 patients with HCC who underwent initial IATs were consecutively enrolled. These patients were divided into training datasets (TD, n = 1700), internal validation datasets (ITD, n = 428), and external validation datasets (ETD, n = 200). Five-years death was used to predict outcome. Thirty-four clinical information were input and five supervised machine learning (ML) algorithms, including eXtreme Gradient Boosting (XGBoost), Categorical Gradient Boosting (CatBoost), Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LGBT), and Random Forest (RF), were compared using the areas under the receiver operating characteristic (AUC) with DeLong test. The variables with top important ML scores were used to build the RSSM by stepwise Cox regression. RESULTS: The CatBoost model achieved the best discrimination when 12 top variables were input, with the AUC of 0.851 (95% confidence intervals (CI), 0.833-0.868) for TD, 0.817 (95%CI, 0.759-0.857) for ITD, and 0.791 (95%CI, 0.748-0.834) for ETD. The RSSM was developed based on the immune checkpoint inhibitors (ICI) (hazard ratios (HR), 0.678; 95%CI 0.549, 0.837), tyrosine kinase inhibitors (TKI) (HR, 0.702; 95%CI 0.605, 0.814), local therapy (HR, 0.104; 95%CI 0.014, 0.747), response to the first IAT (HR, 4.221; 95%CI 2.229, 7.994), tumor size (HR, 1.054; 95%CI 1.038, 1.070), and BCLC grade (HR, 2.375; 95%CI 1.950, 2.894). Kaplan-Meier analysis confirmed the role of RSSM in risk stratification (p < 0.001). CONCLUSIONS: The RSSM can stratify accurately prognostic risk for HCC patients received IAT. On the basis, an online calculator permits easy implementation of this model. CLINICAL RELEVANCE STATEMENT: The risk scoring scale model could be easily implemented for physicians to stratify risk and predict prognosis quickly and accurately, thereby serving as a more favorable tool to strengthen individualized intra-arterial therapies and management in patients with unresectable hepatocellular carcinoma. KEY POINTS: • The Categorical Gradient Boosting (CatBoost) algorithm achieved the optimal and robust predictive ability (AUC, 0.851 (95%CI, 0.833-0.868) in training datasets, 0.817 (95%CI, 0.759-0.857) in internal validation datasets, and 0.791 (95%CI, 0.748-0.834) in external validation datasets) for prediction of 5-years death of hepatocellular carcinoma (HCC) after intra-arterial therapies (IATs) among five machine learning models. • We used the SHapley Additive exPlanations algorithms to explain the CatBoost model so as to resolve the black boxes of machine learning principles. • A simpler restricted variable, risk scoring scale model (RSSM), derived by stepwise Cox regression for risk stratification after intra-arterial therapies for hepatocellular carcinoma, provides the potential forewarning to adopt combination strategies for high-risk patients.

Construction of a Prognostic Nomogram for Major Amputation Within 30 Days Postrevascularization in Patients With Acute Lower Limb Ischemia Based on 2D Perfusion Parameters.

PURPOSE: The purpose of the study is to develop a prediction model for major amputation (MA) within 30 days after arterial revascularization in patients with acute lower limb ischemia (ALLI) using 2-dimensional (2D) perfusion imaging parameters. MATERIALS AND METHODS: A retrospective study was performed in ALLI patients undergoing arterial revascularization between October 2015 and May 2022. Patients were randomly assigned into training and validation cohorts in a ratio of 7:3. Variables were selected using univariate and multivariate logistic regression. A nomogram for the MA risk within 30 days after arterial revascularization in ALLI patients was created. Its discrimination, calibration, and clinical effectiveness were reported. RESULTS: A total of 310 ALLI patients (326 limbs) were included. The MA rate within 30 days after arterial revascularization was 11.6%. Skin speckle, myoglobin, and time-to-peak were independent risk factors, while atrial fibrillation was a protective factor (all p<0.05). The nomogram predicted 30-day MA with satisfactory discriminative ability. The integrated discrimination improvement was 0.279 and 0.379 for the training and validation cohorts, respectively (both p<0.001). Calibration curves were close to the standard curve. The decision curve analysis demonstrated net benefits. CONCLUSION: This 2D perfusion imaging parameter-based nomogram could accurately predict the risk of MA within 30 days postrevascularization in ALLI patients. CLINICAL IMPACT: This study introduces a novel nomogram based on 2-dimensional (2D) perfusion imaging that can significantly advance the prognosis prediction in ALLI patients. By calculating the risk of major amputation within 30 days postrevascularization, this nomogram offers an accurate predictive tool and can lead to more informed decision-making on patient management. The innovative aspect of this research lies in its utilization of 2D perfusion parameters, a novel approach that enhances risk assessment accuracy in ALLI patients. This nomogram represents a significant step toward risk stratification and can guide future research for appropriate management on ALLI patients with different risk profiles.

Cytosolic DNA initiates a vicious circle of aging-related endothelial inflammation and mitochondrial dysfunction via STING: the inhibitory effect of Cilostazol.

Endothelial senescence, aging-related inflammation, and mitochondrial dysfunction are prominent features of vascular aging and contribute to the development of aging-associated vascular disease. Accumulating evidence indicates that DNA damage occurs in aging vascular cells, especially in endothelial cells (ECs). However, the mechanism of EC senescence has not been completely elucidated, and so far, there is no specific drug in the clinic to treat EC senescence and vascular aging. Here we show that various aging stimuli induce nuclear DNA and mitochondrial damage in ECs, thus facilitating the release of cytoplasmic free DNA (cfDNA), which activates the DNA-sensing adapter protein STING. STING activation led to a senescence-associated secretory phenotype (SASP), thereby releasing pro-aging cytokines and cfDNA to further exacerbate mitochondrial damage and EC senescence, thus forming a vicious circle, all of which can be suppressed by STING knockdown or inhibition. Using next-generation RNA sequencing, we demonstrate that STING activation stimulates, whereas STING inhibition disrupts pathways associated with cell senescence and SASP. In vivo studies unravel that endothelial-specific Sting deficiency alleviates aging-related endothelial inflammation and mitochondrial dysfunction and prevents the development of atherosclerosis in mice. By screening FDA-approved vasoprotective drugs, we identified Cilostazol as a new STING inhibitor that attenuates aging-related endothelial inflammation both in vitro and in vivo. We demonstrated that Cilostazol significantly inhibited STING translocation from the ER to the Golgi apparatus during STING activation by targeting S162 and S243 residues of STING. These results disclose the deleterious effects of a cfDNA-STING-SASP-cfDNA vicious circle on EC senescence and atherogenesis and suggest that the STING pathway is a promising therapeutic target for vascular aging-related diseases. A proposed model illustrates the central role of STING in mediating a vicious circle of cfDNA-STING-SASP-cfDNA to aggravate age-related endothelial inflammation and mitochondrial damage.

Therapeutic effects of focused ultrasound on vulvar squamous intraepithelial lesions in rat.

OBJECTIVE: In this study, we established a Sprague-Dawley rat model of vulvar squamous intraepithelial lesions and investigated the impact of focused ultrasound on the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and mutant type p53 (mtp53) in the vulvar skin of rats with low-grade squamous intraepithelial lesions (LSIL). MATERIALS AND METHODS: The vulvar skin of 60 rats was treated with dimethylbenzanthracene (DMBA) and mechanical irritation three times a week for 14 weeks. Rats with LSIL were randomly allocated into the experimental group or the control group. The experimental group was treated with focused ultrasound, while the control group received sham treatment. RESULTS: After 14 weeks treatment of DMBA combined with mechanical irritation, LSIL were observed in 44 (73.33%) rats, and high-grade squamous intraepithelial lesions (HSIL) were observed in 14 (23.33%) rats. 90.91% (20/22) of rats showed normal pathology and 9.09% (2/22) of rats exhibited LSIL in the experimental group at four weeks after focused ultrasound treatment. 22.73% (5/22) of rats exhibited LSIL, 77.27% (17/22) of rats progressed to HSIL in the control group. Compared with the control-group rats, the levels of HIF-1α, VEGF and mtp53 were significantly decreased in experimental-group rats (p < 0.05). CONCLUSIONS: These results indicate that DMBA combined with mechanical irritation can induce vulvar squamous intraepithelial lesion in SD rats. Focused ultrasound can treat LSIL safely and effectively, prevent the progression of vulvar lesions, and improve the microenvironment of vulvar tissues by decreasing the localized expression of HIF-1α, VEGF, and mtp53 in rats.

Feasibility study of focused ultrasound in the treatment of vulvar low-grade squamous intraepithelial lesions with persistent symptoms.

OBJECTIVE: This study aimed to investigate the feasibility, efficacy, and safety of focused ultrasound (FUS) for the treatment of vulvar low-grade squamous intraepithelial lesions (VLSIL) with persistent symptoms. METHODS: This retrospective analysis included 24 VLSIL patients who underwent FUS treatment. At each follow-up visit, the clinical response was assessed including changes in symptoms and signs. In addition, the histological response was assessed based on the vulvar biopsy results of the 3rd follow-up. Clinical and histological response were assessed to elucidate the efficacy. RESULTS: A total of 22 patients completed follow-up and post-treatment pathological biopsies. After treatment, the clinical scores of itching decreased from 2.55 ± 0.51 to 0.77 ± 0.81 (p < 0.05). Furthermore, the clinical response rate and histological response rate were 86.4% and 81.8%, respectively. Only two cured patients indicated recurrence in the 3rd and 4th year during the follow-up period and achieved cure after re-treatment. In terms of adverse effects, only one patient developed ulcers after treatment, which healed after symptomatic anti-inflammatory treatment without scarring, and no other treatment complications were found in any patients. None of the patients developed a malignant transformation during the follow-up period. CONCLUSION: This study revealed that FUS is feasible, effective, and safe for treating VLSIL patients with persistent symptoms, providing a new solution for the noninvasive treatment of symptomatic VLSIL.

Elucidating the intricacies of the H2S signaling pathway in gasotransmitters: Highlighting the regulation of plant thiocyanate detoxification pathways.

In recent decades, there has been increasing interest in elucidating the role of sulfur-containing compounds in plant metabolism, particularly emphasizing their function as signaling molecules. Among these, thiocyanate (SCN-), a compound imbued with sulfur and nitrogen, has emerged as a significant environmental contaminant frequently detected in irrigation water. This compound is known for its potential to adversely impact plant growth and agricultural yield. Although adopting exogenous SCN- as a nitrogen source in plant cells has been the subject of thorough investigation, the fate of sulfur resulting from the assimilation of exogenous SCN- has not been fully explored. There is burgeoning curiosity in probing the fate of SCN- within plant systems, especially considering the possible generation of the gaseous signaling molecule, hydrogen sulfide (H2S) during the metabolism of SCN-. Notably, the endogenous synthesis of H2S occurs predominantly within chloroplasts, the cytosol, and mitochondria. In contrast, the production of H2S following the assimilation of exogenous SCN- is explicitly confined to chloroplasts and mitochondria. This phenomenon indicates complex interplay and communication among various subcellular organelles, influencing signal transduction and other vital physiological processes. This review, augmented by a small-scale experimental study, endeavors to provide insights into the functional characteristics of H2S signaling in plants subjected to SCN--stress. Furthermore, a comparative analysis of the occurrence and trajectory of endogenous H2S and H2S derived from SCN--assimilation within plant organisms was performed, providing a focused lens for a comprehensive examination of the multifaceted roles of H2S in rice plants. By delving into these dimensions, our objective is to enhance the understanding of the regulatory mechanisms employed by the gasotransmitter H2S in plant adaptations and responses to SCN--stress, yielding invaluable insights into strategies for plant resilience and adaptive capabilities.

Boron deficiency decreased the root activity of Ga-exposed rice seedlings by reducing iron accumulation and increasing Ga in iron plaque.

Gallium (Ga) is an emerging chemical pollutant chiefly associated with high-tech industries. Boron (B) alleviates the negative effects of toxic elements on plant growth. Thereby, the effects of B fertilization on Ga toxicity in rice seedlings was studied to clarify the role of iron plaque in the distribution of Ga, Fe, and B in Ga-treated rice seedlings in the presence or absence of B. Gallium exposure significantly reduced the biomass of rice seedlings. Boron deficiency induced a significant change in the distribution of B in Ga-treated rice seedlings compared with "Ga+B" treatments. Accumulation of Ga in roots, dithionite-citrate-bicarbonate (DCB) extracts, and shoots showed a dose-dependent manner from both +B and -B rice seedlings. Boron nutrition levels affect the distribution of Fe in roots, DCB extracts, and shoots, in which DCB-extractable Fe was significantly decreased from "Ga-B" treatments compared with "Ga+B" treatments. Root activity was significantly decreased in both Ga-exposed rice seedlings; however, B-deficient seedlings showed a severe reduction than +B rice seedlings. These results reveal that Fe plaque might be a temporary sink for B accumulation when plants are grown with proper B, wherein the re-utilization of DCB-extractable B stored in Fe plaque is mandatory for plant growth under B deficiency. Correlation analysis revealed that B deficiency decreased the root activity of Ga-exposed rice seedlings by reducing DCB-extractable Fe and increasing DCB-extractable Ga in Fe plaque. This study enhances our understanding of how B nutritional levels affect Ga toxicity in rice plants.

Expanding the Hydrophobic Cavity Surface of Azocalix[4]arene to Enable Biotin/Avidin Affinity with Controlled Release.

The development of artificial receptors that combine ultrahigh-affinity binding and controllable release for active guests holds significant importance in biomedical applications. On one hand, a complex with an exceedingly high binding affinity can resist unwanted dissociation induced by dilution effect and complex interferents within physiological environments. On the other hand, stimulus-responsive release of the guest is essential for precisely activating its function. In this context, we expanded hydrophobic cavity surface of a hypoxia-responsive azocalix[4]arene, affording Naph-SAC4A. This modification significantly enhanced its aqueous binding affinity to 1013 M-1, akin to the naturally occurring strongest recognition pair, biotin/(strept-)avidin. Consequently, Naph-SAC4A emerges as the first artificial receptor to simultaneously integrate ultrahigh recognition affinity and actively controllable release. The markedly enhanced affinity not only improved Naph-SAC4A's sensitivity in detecting rocuronium bromide in serum, but also refined the precision of hypoxia-responsive doxorubicin delivery at the cellular level, demonstrating its immense potential for diverse practical applications.

High power optical frequency comb with 10-19 frequency instability.

Optical frequency combs with more than 10 W have paved the way for extreme ultraviolet combs generation by interaction with inert gases, leading to extreme nonlinear spectroscopy and the ultraviolet nuclear clock. Recently, the demand for an ultra-long-distance time and frequency space transfer via optical dual-comb proposes a new challenge for high power frequency comb in respect of power scaling and optical frequency stability. Here we present a frequency comb based on fiber chirped pulse amplification (CPA), which can offer more than 20 W output power. We further characterize the amplifier branch noise contribution by comparing two methods of locking to an optical reference and measure the out-of-loop frequency instability by heterodyning two identical high-power combs. Thanks to the low noise CPA, reasonable locking method, and optical path-controlled amplifiers, the out-of-loop beat note between two combs demonstrates the unprecedented frequency stability of 4.35 × 10-17 at 1s and 6.54 × 10-19 at 1000 s.

Using red blood cell distribution width to predict death after abdominal aortic aneurysm rupture.

BACKGROUND: An abdominal aortic aneurysm is a life-threatening enlargement in the major vessel at the abdomen level. This study investigated the associations between different levels of red blood cell distribution width and all-cause mortality among patients with abdominal aortic aneurysm rupture. It developed predictive models for all-cause mortality risk. METHODS: This was a retrospective cohort study using 2001 to 2012 MIMIC-III dataset. The study sample included 392 U.S. adults with abdominal aortic aneurysms who were admitted to ICU after the aneurysm rupture. Then we used two single-factor and four multivariable logistic regression models to examine the associations between different levels of red blood cell distribution and all-cause mortality (30 days and 90 days), controlling for demographics, comorbidities, vital signs, and other laboratory measurements. The receiver operator characteristic curves were calculated, and the areas under the curves were recorded. RESULTS: There were 140 (35.7%) patients with an abdominal aortic aneurysm in the red blood cell distribution width range between 11.7 and 13.8%, 117 (29.8%) patients in the range between 13.9 and 14.9%, and 135 (34.5%) patients in the range between 15.0 and 21.6%. Patients with higher red blood cell distribution width level (> 13.8%) tended to have a higher mortality rate (both 30 days and 90 days), congestive heart failure, renal failure, coagulation disorders, lower hemoglobin, hematocrit, MCV, red blood cell count, higher levels of chloride, creatinine, sodium, and BUN (All P < 0.05). Results of multivariate logistic regression models indicated that patients with higher red blood cell distribution width levels (> 13.8%) had the highest statistically significant odd ratios of 30 days and 90 days of all-cause mortality than lower red blood cell distribution width levels. The area under the RDW curve was lower (P = 0.0009) than that of SAPSII scores. CONCLUSIONS: Our study found that patients with abdominal aortic aneurysm rupture with a higher blood cell distribution had the highest risk of all-cause mortality. Using the blood cell distribution width level in patients with abdominal aortic aneurysm rupture to predict mortality should be considered in future clinical practice.

Attributes underlying patient choice of treatment modality for low-grade squamous intraepithelial lesion complicated by high-risk human papillomavirus infection.

OBJECTIVE: To use logistic regression to analyze the attributes underlying patients' treatment options for low-grade squamous intraepithelial lesion (LSIL) complicated with high-risk human papillomavirus (HR-HPV) infection, and identify the best benefit group of different treatment options. METHODS: Clinical data of 197 LSIL patients with HR-HPV infection between June 2009 and February 2022 were collected. According to the treatment options chosen by the patients, they were divided into the interferon, photodynamic therapy, follow-up observation, and focused ultrasound (FUS) treatment groups. One-way analysis of variance (ANOVA) and multivariate logistic regression analysis were used to analyze the influencing factors, including age, occupation, education level, maternity history, reason for encounter, route of consultation, annual personal and household income, screening for related risk factors, and identifying the best benefit group of different treatment options. RESULTS: One-way ANOVA revealed a statistically significant difference in age, education level, maternity history, reason for encounter, and annual household income (p < 0.05). Multivariate logistic regression analysis was performed on these five factors, indicating that age ≤35 years, high school educational level or higher, and no childbirth history were independent risk factors influencing patients' choices of FUS treatment. The receiver operating characteristic curve was used to determine the age threshold of 31 years. CONCLUSION: Age, educational level, and maternity history were independent risk factors influencing patients' choice of treatment modality for LSIL complicated with HR-HPV infection. Age ≤31 years, high school, equivalent, or higher educational level, and no childbirth yielded a higher rate of choosing FUS treatment for LSIL patients with HR-HPV infection.

Comparison of the efficacy of focused ultrasound at different focal depths in treating vulvar lichen sclerosus.

OBJECTIVE: This study aimed to compare the efficacy and safety of focused ultrasound (FU) at different focal depths in treating vulvar lichen sclerosus (VLS). METHODS: A retrospective study was conducted on 84 patients with VLS. Among them, 43 cases were treated with FU at a focal depth of 2.5 mm and 41 cases at a focal depth of 4.0 mm. Therapeutic time, treatment energy, postoperative efficacy, complications and recurrence rates were compared. RESULTS: No statistically substantially differences in age, disease course, history of immune system diseases, lesion size and severity of symptoms were found between the two groups. All patients successfully received FU therapy. No significant difference in curative rate was observed between the two groups at 3, 6 and 12 months after FU therapy. At 12 months after FU therapy, the recurrence rate of the experimental group (FU treatment at 2.5 mm focal depth) was lower than the control group (FU treatment at 4.0 mm focal depth) (7.0% vs 24.4%, p = 0.027). The experimental group was treated for a shorter period of time [22.69 ± 0.64 (min) vs 24.93 ± 0.72(min), p = 0.022] and at a lower dose[5,026.05 ± 148.00(J) vs 5,484.26 ± 160.60(J) p = 0.039]. CONCLUSION: Compared with that at the routine focal depth (4.0 mm), FU therapy at a low treatment depth (2.5 mm) can achieve a similar therapeutic effect but lower recurrence rate, therapeutic time and treatment energy. This work provides insight into the optimization of clinical protocols.

A Clinical Series in Patients with Naso-Pharyngeal Cancer and Their Outcomes with Stent Graft Treatment for Sentinel Bleeding to Prevent Frank Carotid Rupture.

BACKGROUND: The purpose of this study was to evaluate the safety and effectiveness of heparin-bonded VIABAHN stent graft for carotid rupture in patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 1,596 patients with NPC were enrolled. Fifteen patients (8 male and 7 female), who developed carotid artery rupture (CAR) after radiotherapy between January 2016 and June 2019, were retrospectively analyzed. Complications and mortality were assessed at 12 months postoperatively. RESULTS: The incidence of carotid burst syndrome in the NPC cohort was 0.94%. The distribution of site of arterial rupture was as follows: common carotid artery (4 cases), C1 segment of internal carotid artery (8 cases), and C2 segment of internal carotid artery (3 cases). All patients successfully underwent emergency deployment of the heparin-bonded VIABAHN to seal off the ruptured carotid artery. The survival rate as of 12-month follow-up was 80.0%. Three patients died of short-term rebleeding, lung infection, and tumor progression. No stent-related complications occurred in our cohort. CONCLUSIONS: Heparin-bonded VIABAHN-covered stents may be a safe and effective treatment option for carotid rupture in patients with NPC.

Baicalein inhibits apoptosis and autophagy induced by chlorpyrifos exposure to kidney of Cyprinus carpio through activation of PI3K/AKT pathway.

Chlorpyrifos (CPF), a widely used organophosphate pesticide that has caused large-scale contamination globally, has become a major concern. Baicalein (BAI), as a flavonoid extract, shows anti-inflammatory as well as antioxidant activities. The kidneys of fish serve to excrete toxins and are major target organs for environmental contaminants. However, it is not obvious whether BAI can counteract the damage caused by CPF exposure to fish kidneys. Therefore, we conducted a 30-day simulation of CPF poisoning and/or BAI treatment by adding 23.2 µg/L CPF to water and/or 0.15 g/kg BAI to feed. In the transmission electron microscopy results, we observed obvious phenomenon of autophagy and apoptosis in the CPF group, and the TUNEL staining and immunofluorescence of LC3B and p62 double-staining results confirmed that CPF induced autophagy and apoptosis in the kidney of common carp. Furthermore, CPF induced the increase of ROS level and inhibition of PI3K and Nrf2 pathways, which in turn triggered oxidative stress, autophagy and apoptosis in carp kidney according to western blot, RT-qPCR and kit assays. However, addition of BAI significantly alleviated oxidative stress, autophagy and apoptosis due to binding to PI3K protein. Additionally, through phylogenetic tree and structural domain analyses, we also found that the binding sites of BAI and PI3K are conserved in a variety of representative species. These results suggest that BAI antagonizes CPF-caused renal impairments in carp involving the PI3K/AKT pathway and the Nrf2 pathway. Our findings provide new insights into the nephrotoxicity effects of CPF and the potential use of BAI as a detoxification agent for CPF intoxication.

A multitask deep learning radiomics model for predicting the macrotrabecular-massive subtype and prognosis of hepatocellular carcinoma after hepatic arterial infusion chemotherapy.

BACKGROUND: The macrotrabecular-massive (MTM) is a special subtype of hepatocellular carcinoma (HCC), which has commonly a dismal prognosis. This study aimed to develop a multitask deep learning radiomics (MDLR) model for predicting MTM and HCC patients' prognosis after hepatic arterial infusion chemotherapy (HAIC). METHODS: From June 2018 to March 2020, 158 eligible patients with HCC who underwent surgery were retrospectively enrolled in MTM related cohorts, and 752 HCC patients who underwent HAIC were included in HAIC related cohorts during the same period. DLR features were extracted from dual-phase (arterial phase and venous phase) contrast-enhanced computed tomography (CECT) of the entire liver region. Then, an MDLR model was used for the simultaneous prediction of the MTM subtype and patient prognosis after HAIC. The MDLR model for prognostic risk stratification incorporated DLR signatures, clinical variables and MTM subtype. FINDINGS: The predictive performance of the DLR model for the MTM subtype was 0.968 in the training cohort [TC], 0.912 in the internal test cohort [ITC] and 0.773 in the external test cohort [ETC], respectively. Multivariable analysis identified portal vein tumor thrombus (PVTT) (p = 0.012), HAIC response (p < 0.001), HAIC sessions (p < 0.001) and MTM subtype (p < 0.001) as indicators of poor prognosis. After incorporating DLR signatures, the MDLR model yielded the best performance among all models (AUC, 0.855 in the TC, 0.805 in the ITC and 0.792 in the ETC). With these variables, the MDLR model provided two risk strata for overall survival (OS) in the TC: low risk (5-year OS, 44.9%) and high risk (5-year OS, 4.9%). INTERPRETATION: A tool based on MDLR was developed to consider that the MTM is an important prognosis factor for HCC patients. MDLR showed outstanding performance for the prognostic risk stratification of HCC patients who underwent HAIC and may help physicians with therapeutic decision making and surveillance strategy selection in clinical practice.

Effect of hydrocolloid dressing combined with low molecular weight heparin and calcium on scar hyperplasia in burn patients with venous thromboembolism.

The purpose of this study is to investigate the effect of hydrocolloid dressing combined with low molecular weight heparin calcium on scar hyperplasia in burn patients with venous thromboembolism. A retrospective analysis was made on 98 patients with burns complicated with venous thromboembolism in Renmin Hospital, Hubei University of Medicine from January 2020 to April 2021. According to different treatment methods, they were divided into a control group (48 cases) and a research group (50 cases), who were given low molecular weight heparin calcium combined with routine treatment and hydrocolloid dressing on the basis of the control group. The wound healing time, dressing change times and infection symptom regression time in the study group were significantly lower than those in the control group (P < .05). After the intervention, the degree of wound pain in both groups was reduced, and the degree of wound pain in the study group was significantly lower than that in the control group, with statistical significance (P < .05). Fibrinogen, activated partial thromboplastin (APPT), D-dimer, fibrinolytic degradation products, prothrombin time and activated partial prothrombin time of the two groups were all improved. The degree of scar hyperplasia in both groups was improved, and the degree of scar hyperplasia in the study group was significantly better than that in the control group, and the difference was statistically significant (P>.05). Complications in the study group were lower than those in the control group, and the difference was statistically significant (P < .05). The hydrocolloid dressing combined with low molecular weight heparin calcium can effectively shorten the wound healing time and infection symptom regression time of burn patients with venous thromboembolism, reduce the number of dressing changes, reduce the degree of pain, have no influence on coagulation function, reduce the degree of scar, and reduce the incidence of complications.

2D perfusion angiography: an alternative method to evaluate endovascular intervention for acute lower limb ischemia.

BACKGROUND: Despite advances in endovascular techniques to treat acute limb ischemia (ALI), evaluation of clinical outcomes for revascularization remains challenging, especially the accurate quantification of post-endovascular limb perfusion. This study aimed to investigate the accuracy and value of 2D perfusion angiography to evaluate endovascular intervention for ALI. METHODS: A total of 47 patients with ALI were retrospectively analyzed. The transcutaneous oxygen partial pressure (TcPO2) was obtained using laser Doppler blood perfusion monitoring. The ankle-brachial index (ABI) and angiographic images were obtained before and after endovascular intervention. iFlow imaging was used to obtain color-coded images. Regions of interest (ROIs) at the femoral head, knee joint, and ankle joint were selected to obtain the time to peak (TTP). The differences in the TTP between the knee and femoral head regions (TTP difference in the knee area) and between the ankle and knee regions (TTP difference in the ankle area) were observed. The TTP, ABI, and TcPO2 between the complete response (CR), partial response (PR), no response (NR), and amputation (AM) groups were compared. The correlation between TTP changes in the ankle area (ΔTTP) and changes in ABI (ΔABI)/changes in TcPO2 (ΔTcPO2) was analyzed. RESULTS: There was a significant increase in both TcPO2 and ABI compared with the pre-intervention values (27.75 ± 5.32 vs 40.92 ± 4.62, and 0.35 ± 0.16 vs 0.79 ± 0.15, respectively, all p < 0.01). The post-intervention TTP differences in the knee areas (5.12 ± 2.45 s) and ankle areas (6.93 ± 4.37 s) were significantly faster than pre-intervention TTP differences (7.03 ± 2.57 s and 10.66 ± 4.07 s, respectively, all p < 0.05). The post-operative TTP in the ankle area, post-operative TTP difference in the ankle area, and ΔTTP in the AM group were higher than the values in the CR and PR groups. The ΔTTP demonstrated strong correlation with ΔABI (r = -0.722, p < 0.01) and ΔTcPO2 (r = -0.734, p < 0.01). CONCLUSIONS: 2D perfusion angiography with enhanced visual and quantitative analysis exhibits great potential to evaluate the efficacy of endovascular intervention, and provides a quantitative and sensitive tool to evaluate post-endovascular limb perfusion for ALI patients.