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In recent years, researchers have highly observed that neurological disorders (NSDs) with the aging of the population are a global health burden whose prevalence is increasing every year. Previous evidence suggested that the occurrence of neurological disorders is correlated with predisposing factors such as inflammation, aging, and injury. Particularly, the neuronal cells are susceptible to oxidative stress, leading to lesions caused by high oxygen-consuming properties. Oxidative stress (OS) is a state of peroxidation, which occurs as a result of the disruption of the balance between oxidizing and antioxidizing substances. The oxidative intermediates such as free radicals, hydrogen peroxide (H2O2), and superoxide anion (O2-) produced by OS promote disease progression. Curcumin, a natural diketone derived from turmeric, is a natural antioxidant with a wide range of neuroprotective, anti-inflammatory, anti-tumor, anti-aging, and antioxidant effects. Fortunately, curcumin is recognized for its potent antioxidant properties and is considered a promising candidate for the prevention and treatment of neurological diseases. Consequently, this review elucidates the mechanisms by which curcumin mitigates oxidative stress and emphasizes the potential in treating nervous system disorders, including depression, Alzheimer’s disease, Parkinson’s disease, epilepsy, subarachnoid hemorrhage, and glioblastoma. We aim to provide a new therapeutic option for the management of neurological diseases.

Abstract Immunosenescence increases the risk and severity of diseases in elderly individuals and leads to impaired vaccine-induced immunity. With aging of the global population and the emerging risk of epidemics, developing adjuvants and vaccines for elderly individuals to improve their immune protection is pivotal for healthy aging worldwide. Deepening our understanding of the role of immunosenescence in vaccine efficacy could accelerate research focused on optimizing vaccine delivery for elderly individuals. In this review, we analyzed the characteristics of immunosenescence at the cellular and molecular levels. Strategies to improve vaccination potency in elderly individuals are summarized, including increasing the antigen dose, preparing multivalent antigen vaccines, adding appropriate adjuvants, inhibiting chronic inflammation, and inhibiting immunosenescence. We hope that this review can provide a review of new findings with regards to the impacts of immunosenescence on vaccine-mediated protection and inspire the development of individualized vaccines for elderly individuals.

BackgroundThe interaction between pyroptosis—a form of programmed cell death—and tumor immunity represents a burgeoning field of interest. Pyroptosis exhibits a dual role in cancer: it can both promote tumor development and counteract it by activating immune responses that inhibit tumor evasion and encourage cell death. Current tumor immunotherapy strategies, notably CAR-T cell therapy and immune checkpoint inhibitors (ICIs), alongside the potential of certain traditional Chinese medicinal compounds, highlight the intricate relationship between pyroptosis and cancer immunity. As research delves deeper into pyroptosis mechanisms within tumor therapy, its application in enhancing tumor immune responses emerges as a novel research avenue.PurposeThis review aims to elucidate the mechanisms underlying pyroptosis, its impact on tumor biology, and the advancements in tumor immunotherapy research.MethodsA comprehensive literature review was conducted across PubMed, Embase, CNKI, and Wanfang Database from the inception of the study until August 22, 2023. The search employed keywords such as “pyroptosis”, “cancer”, “tumor”, “mechanism”, “immunity”, “gasdermin”, “ICB”, “CAR-T”, “PD-1”, “PD-L1”, “herbal medicine”, “botanical medicine”, “Chinese medicine”, “traditional Chinese medicine”, “immunotherapy”, linked by AND/OR, to capture the latest findings in pyroptosis and tumor immunotherapy.ResultsPyroptosis is governed by a complex mechanism, with the Gasdermin family playing a pivotal role. While promising for tumor immunotherapy application, research into pyroptosis’s effect on tumor immunity is still evolving. Notably, certain traditional Chinese medicine ingredients have been identified as potential pyroptosis inducers, meriting further exploration.ConclusionThis review consolidates current knowledge on pyroptosis’s role in tumor immunotherapy. It reveals pyroptosis as a beneficial factor in the immunotherapeutic landscape, suggesting that leveraging pyroptosis for developing novel cancer treatment strategies, including those involving traditional Chinese medicine, represents a forward-looking approach in oncology.

Out-of-hospital cardiac arrest is a major public health problem worldwide due to its high burden and poor outcomes. Despite progress in treatment, patient outcomes remain unsatisfactory, particularly in low-resource settings. The establishment of a registry is the first step towards gaining a comprehensive understanding of prevailing local conditions and identifying potential opportunities for improving patient survival. Here, we provide a narrative review of the BASeline Investigation of Out-of-hospital Cardiac Arrest (BASIC-OHCA), the first national OHCA registry in China, to introduce its development history, current state, challenges and future directions. We aim to enhance cross-cultural understanding by providing insights from China, while also serving as a reference for the implementation of large-scale registries in low-resource settings.

Abstract Background Pregnant women belong to the special population of drug therapy, and their physiological state, pharmacokinetics and pharmacodynamics are significantly different from the general population. Drug safety during pregnancy involves two generations, which is a hot issue widely concerned in the whole society. Global Trigger Tool (GTT) of the Institute for Healthcare Improvement (IHI) has been wildly used as a patient safety measurement strategy by several institutions and national programs, and the effectiveness had been demonstrated. But only one study reports the use of GTT in obstetric delivery until now. The aim of the study is to establish triggers detecting adverse drug events (ADEs) suitable for obstetric inpatients on the basis of the GTT, to examine the performance of the obstetric triggers in detecting ADEs experienced by obstetric units compared with the spontaneous reporting system and GTT, and to assess the utility and value of the obstetric trigger tool in identifying ADEs of obstetric inpatients. Methods Based on a literature review searched in PubMed and CNKI from January of 1997 to October of 2023, retrospective local obstetric ADEs investigations, relevant obstetric guidelines and the common adverse reactions of obstetric therapeutic drugs were involved to establish the initial obstetric triggers. According to the Delphi method, two rounds of expert questionnaire survey were conducted among 16 obstetric and neonatological physicians and pharmacists until an agreement was reached. A retrospective study was conducted to identity ADEs in 300 obstetric inpatient records at the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital from June 1 to September 30, 2018. Two trained junior pharmacists analyzed the first eligible records independently, and the included records reviewed by trained pharmacist and physician to identify ADEs. Sensitivity and specificity of the established obstetric triggers were assessed by the number of ADEs/100 patients and positive predictive value with the spontaneous reporting system (SRS) and GTT. Excel 2010 and SPSS22 were used for data analysis. Results Through two rounds of expert investigation, 39 preliminary triggers were established that comprised four modules (12 laboratory tests, 9 medications, 14 symptoms, and 4 outcomes). A total of 300 medical records were reviewed through the obstetric triggers, of which 48 cases of ADEs were detected, with an incidence of ADEs of 16%. Among the 39 obstetric triggers, 22 (56.41%) were positive and 11 of them detected ADEs. The positive predictive value (PPV) was 36.36%, and the number of ADEs/100 patients was 16.33 (95% CI, 4.19–17.81). The ADE detection rate, positive trigger rate, and PPV for the obstetric triggers were significantly augmented, confirming that the obstetric triggers were more specific and sensitive than SRS and GTT. Conclusion The obstetric triggers were proven to be sensitive and specific in the active monitoring of ADE for obstetric inpatients, which might serve as a reference for ADE detection of obstetric inpatients at medical institutions.

Background: Some COVID-19 patients deteriorate to severe cases with relatively higher case-fatality rates, which increases the medical burden. This necessitates identification of patients at risk of severe disease. Early assessment plays a crucial role in identifying patients at risk of severe disease. This study is to assess the effectiveness of SUPER score as a predictor of severe COVID-19 cases. Methods: We consecutively enrolled COVID-19 patients admitted to a comprehensive medical center in Wuhan, China, and recorded clinical characteristics and laboratory indexes. The SUPER score was calculated using parameters including oxygen saturation, urine volume, pulse, emotional state, and respiratory rate. In addition, the area under the receiver operating characteristic curve (AUC), specificity, and sensitivity of the SUPER score for the diagnosis of severe COVID-19 were calculated and compared with the National Early Warning Score 2 (NEWS2). Results: The SUPER score at admission, with a threshold of 4, exhibited good predictive performance for early identification of severe COVID-19 cases, yielding an AUC of 0.985 (95% confidence interval [CI] 0.897–1.000), sensitivity of 1.00 (95% CI 0.715–1.000), and specificity of 0.92 (95% CI 0.775–0.982), similar to NEWS2 (AUC 0.984; 95% CI 0.895–1.000, sensitivity 0.91; 95% CI 0.587–0.998, specificity 0.97; 95% CI 0.858–0.999). Compared with patients with a SUPER score

Objective: In this study, we assessed the efficacy and safety of various thrombolytic treatment protocols in patients with hyperacute cerebral infarction. Methods: Patients diagnosed with acute ischemic stroke within 6 h of symptom onset and with brain computer tomography angiography confirming the absence of major vessel stenosis or occlusion were eligible for this study. The enrolled patients were subsequently randomized into two groups: all the groups received the standard intravenous thrombolysis treatment with rt-PA (0.9 mg/kg), and the experimental group underwent sequential intra-arterial thrombolysis treatment with alteplase (0.3 mg/kg, with a maximum dose of 22 mg), administered directly into the target vessel via a microcatheter. Both groups were closely monitored for changes in their National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin scale score, hemorrhage rate, all-cause mortality rate, and the rate of favorable outcomes at 90 ± 7 days. Results: Ninety-four participants were enrolled in this study, with both the control and experimental groups initiating intravenous injection of rt-PA at a median time of 29 min. For the experimental group, the median time for arterial puncture was 123 min. Baseline data for both groups were similar (P > 0.05). Hemorrhagic transformation occurred in 24.47 % (23 patients), with a lower intracranial hemorrhage rate observed in the experimental group compared to the control group (15.2 % vs 33.3 %, P 0.05). A higher proportion of patients in the experimental group achieved favorable outcomes compared to the control group (87.0 % vs 43.8 %, P

Background: Thromboembolic disease is associated with a high rate of disability or death and gravely jeopardizes people’s health and places considerable financial pressure on society. The primary treatment for thromboembolic illness is anticoagulant medication. Fondaparinux, a parenteral anticoagulant medicine, is still used but is confusing due to its disparate domestic and international indications and lack of knowledge about its usage. Its off-label drug usage in therapeutic settings and irrational drug use are also common.Objective: The aim of this guideline is to enhance the judicious clinical application of fondaparinux by consolidating the findings of evidence-based research on the drug and offering superior clinical suggestions.Methods: Seventeen clinical questions were developed by 37 clinical pharmacy experts, and recommendations were formulated under the supervision of three methodologists. Through methodical literature searches and the use of recommendation, assessment, development and evaluation grading techniques, we gathered evidence.Results: This guideline culminated in 17 recommendations, including the use of fondaparinux for venous thromboembolism (VTE) prevention and treatment, perioperative surgical prophylaxis, specific diseases, special populations, bleeding and overdose management. For different types of VTE, we recommend first assessing thrombotic risk in hospitalized patients and then administering the drug according to the patient’s body mass. In surgical patients in the perioperative period, fondaparinux may be used for VTE prophylaxis, but postoperative use usually requires confirmation that adequate hemostasis has been achieved. Fondaparinux may be used for anticoagulation prophylaxis in patients hospitalized for oncological purposes, in patients with atrial fibrillation (AF) after resuscitation, in patients with cirrhosis combined with portal vein thrombosis (PVT), in patients with antiphospholipid syndrome (APS), and in patients with inflammatory bowel disease (IBD). Fondaparinux should be used with caution in special populations, such as pregnant female patients with a history of heparin-induced thrombocytopenia (HIT) or platelet counts less than 50 × 109/L, pregnant patients with a prethrombotic state (PTS) combined with recurrent spontaneous abortion (RSA), and children. For bleeding caused by fondaparinux, dialysis may partially remove the drug.Conclusion: The purpose of this guideline is to provide all healthcare providers with high-quality recommendations for the clinical use of fondaparinux and to improve the rational use of the drug in clinical practice. Currently, there is a lack of a dedicated antidote for the management of fondaparinux. The clinical investigation of activated prothrombin complex concentrate (APCC) or recombinant activated factor VII (rFⅦa) as potential reversal agents is still pending. This critical gap necessitates heightened scrutiny and research emphasis, potentially constituting a novel avenue for future inquiries into fondaparinux sodium. A meticulous examination of adverse events and safety profiles associated with the utilization of fondaparinux sodium will contribute significantly to a more comprehensive understanding of its inherent risks and benefits within the clinical milieu.

Designing and manufacturing safe and effective vaccines is a crucial challenge for human health worldwide. Research on adjuvant-based subunit vaccines is increasingly being explored to meet clinical needs. Nevertheless, the adaptive immune responses of subunit vaccines are still unfavorable, which may partially be attributed to the immune cascade obstacles and unsatisfactory vaccine design. An extended understanding of the crosstalk between vaccine delivery strategies and immunological mechanisms could provide scientific insight to optimize antigen delivery and improve vaccination efficacy. In this review, we summarized the advanced subunit vaccine delivery technologies from the perspective of vaccine cascade obstacles after administration. The engineered subunit vaccines with lymph node and specific cell targeting ability, antigen cross-presentation, T cell activation properties, and tailorable antigen release patterns may achieve effective immune protection with high precision, efficiency, and stability. We hope this review can provide rational design principles and inspire the exploitation of future subunit vaccines.

Background: venous thromboembolism (VTE) is one of the most common complications after major orthopaedic surgery. Recent studies have suggested that aspirin may also be effective in preventing VTE, but it is still controversial whether it can be routinely used.Objectives: To compare the efficacy and safety of aspirin against oral anticoagulants in the prevention of VTE following total hip arthroplasty (THA), total knee arthroplasty (TKA) or hip fracture surgery (HFS).Methods: Relevant publications have been obtained using electronic search databases such as PubMed, Embase, Web of Science, Cochrane Library, and Clinical Trials. gov. from inception to 20 July 2023. Only RCTs evaluating the efficacy and safety of aspirin compared with oral anticoagulants undergoing major orthopaedic surgery were included in the meta-analysis. The primary outcome reported was any VTE event (including deep vein thrombosis (DVT) and pulmonary embolism (PE)). Secondary outcomes included mortality, major bleeding (including gastrointestinal bleed, cerebrovascular hemorrhage, or any bleeding requiring a return to the theater), minor bleeding (ecchymosis, epistaxis, hematuria), and wound complications. The risk of bias for all included studies was assessed according to the Cochrane Collaboration’s tool.Results: After screening 974 studies, 12 randomized clinical trials (RCTs) were included, involving 5,088 participants, including 2,540 participants in aspirin, 2,205 participants in rivaroxaban, and 323 participants in warfarin. Aspirin was found to be less effective than oral anticoagulants in thromboprophylaxis after major orthopedic surgery (RR = 1.206, 95% CI 1.053–1.383). After subgroup analysis according to the type of oral anticoagulant, the results showed that aspirin was similar to rivaroxaban and inferior to warfarin. Considering that the studies in the warfarin group were all conducted before 2000, our results need to be further confirmed. In addition, the aspirin group had a higher risk of VTE than the control group in other subgroups, including a follow-up time of ≤3 months, type of procedure as TKA, high-dose aspirin (≥650 mg qd), and no combined use of mechanical prophylaxis. In terms of safety events, aspirin did not show significant differences in major bleeding (RR = 0.952, 95% CI 0.499–1.815), all-cause mortality (RR = 1.208, 95% CI 0.459–3.177), and wound-related events (RR = 0.618, 95% CI 0.333–1.145) compared with oral anticoagulants, and aspirin was associated with a reduction in the risk of minor bleeding (RR = 0.685, 95% CI 0.552–0.850) events and total bleeding (RR = 0.726, 95% CI 0.590–0.892).Conclusion: Aspirin reduces bleeding risk after major orthopedic surgery compared with oral anticoagulants, but may sacrifice VTE prevention to some extent. Updated evidence is needed to analyze the thromboprophylaxis effects of aspirin in patients undergoing major orthopedic surgery.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=463481, identifier CRD42023463481.

BackgroundDespite the significant progress made in radiotherapy and chemotherapy for the treatment of cervical cancer, patients with lymph node metastasis still have a poor prognosis. It is widely accepted that lymph node metastasis plays a crucial role in the spread of cancer to other organs and is considered an independent factor in predicting a poor prognosis. However, recent research suggests that the importance of lymph nodes in tumor therapy needs to be reevaluated, as preserving the integrity of lymph nodes before immunotherapy can enhance treatment effectiveness.Case presentationIn this report, we present two cases of advanced cervical cancer patients with giant metastatic lymph node lesions in the neck. These patients were effectively treated with a combination of local radiotherapy and immunotherapy after conventional chemoradiotherapy had failed. The combination therapy resulted in significant clinical improvements, with patient 1 achieving over 12 months of progression-free survival (PFS) and patient 2 maintaining sustained remission for an impressive 24 months.ConclusionsThe combination of local radiotherapy and immunotherapy shows promise as a viable treatment option for cervical cancer patients with distant lymph node metastasis, and the giant lymph node metastases may play an important role in this process, which might provide a new opportunity for cancer radioimmunotherapy.

Soluble guanylate cyclase agonists and guanylate cyclase C agonists are two popular drugs for diseases of the cardiovascular system and digestive systems. The common denominator in these conditions is the potential therapeutic target of guanylate cyclase. Thanks to in-depth explorations of their underlying signaling mechanisms, the targets of these drugs are becoming clearer. This review explains the recent research progress regarding potential drugs in this class by introducing representative drugs and current findings on them.

IntroductionThe guidelines' recommendations for anticoagulation in cancer patients with catheter-related thrombosis are unclear. The aim of this systematic review was to assess anticoagulation management in cancer patients with catheter-related thrombosis (CRT) based on previously published studies.MethodsAs of June 10, 2023,we searched databases including PubMed, Embase, and Cochrane and included 11 observational studies that met the criteria. We evaluated 770 adults with active cancer and objectively confirmed patients with CRT who were using drugs including warfarin, LMWH, and new oral anticoagulants as antithrombotic therapy.ResultsWe extracted outcome data, including thrombosis recurrence, catheter dysfunction, major bleeding, and death, and performed a meta-analysis.DiscussionIn this study we found that the risk of VTE recurrence was higher with rivaroxaban, the risk of bleeding and death appeared to be greater with warfarin, and although the risk of catheter dysfunction due to LMWH is a concern, it is still a more reasonable option for cancer patients with catheter-related thrombosis.Systematic Review Registrationhttp://www.clinicaltrials.gov, identifier (CRD42022367979).

The use of affine maneuver control to maintain the desired configuration of unmanned aerial vehicle (UAV) swarms has been widely practiced. Nevertheless, the lack of capability to interact with obstacles and navigate autonomously could potentially limit its extension. To address this problem, we present an innovative formation flight system featuring a virtual leader that seamlessly integrates global control and local control, effectively addressing the limitations of existing methods that rely on fixed configuration changes to accommodate real-world constraints. To enhance the elasticity of an algorithm for configuration change in an obstacle-laden environment, this paper introduces a second-order differentiable virtual force-based metric for planning local trajectories. The virtual field comprises several artificial potential field (APF) forces that adaptively adjust the formation compared to the existing following control. Then, a distributed and decoupled trajectory optimization framework that considers obstacle avoidance and dynamic feasibility is designed. This novel multi-agent agreement strategy can efficiently coordinate the global planning and local trajectory optimizations of the formation compared to a single method. Finally, an affine-based maneuver approach is employed to validate an optimal formation control law for ensuring closed-loop system stability. The simulation results demonstrate that the proposed scheme improves track accuracy by 32.92% compared to the traditional method, while also preserving formation and avoiding obstacles simultaneously.

BackgroundElderly patients frequently experience a high incidence of adverse drug events (ADEs) due to the coexistence of multiple diseases, the combination of various medications, poor medication compliance, and other factors. Global Trigger Tool (GTT) is a new method for identifying ADEs, introducing the concept of a trigger, that is, clues including abnormal laboratory values, reversal drugs, and clinical symptoms that may suggest ADEs, and specifically locating information related to ADEs in the medical record to identify ADEs. The aim of this study was to establish a GTT-based trigger tool for adverse medication events in elderly patients and to investigate the risk variables associated with such events.MethodsThe triggers were identified by reviewing the frequency of ADEs in elderly patients in Sichuan, China, retrieving relevant literature, and consulting experts. A retrospective analysis was carried out to identify adverse medication occurrences among 480 elderly inpatients in Sichuan People’s Hospital.ResultsA total of 56 ADEs were detected in 51 patients (10.62%), 13.04 per 1,000 patient days, and 11.67 per 100 admissions. The overall positive predictive value (PPV) of the triggers was 23.84, and 94.64% of ADEs caused temporary injury. Gastrointestinal system injury (27.87%) and metabolic and nutritional disorders (24.53%) were the primary organ-systems affected by ADEs. The majority of ADEs were caused by drugs used to treat cardiovascular diseases. 71.43% of ADE occurred within 2 days of administration and the risk factor analysis of ADE revealed that the number of medicines had a significant correlation.ConclusionThis study demonstrated GTT’s value as a tool for ADEs detection in elderly inpatients in China. It enhances the level of medication management and comprehensively reflects the situation of ADE of the elderly.

Cardiac fibrosis is a common pathophysiological remodeling process that occurs in a variety of cardiovascular diseases and greatly influences heart structure and function, progressively leading to the development of heart failure. However, to date, few effective therapies for cardiac fibrosis exist. Abnormal proliferation, differentiation, and migration of cardiac fibroblasts are responsible for the excessive deposition of extracellular matrix in the myocardium. Acetylation, a widespread and reversible protein post-translational modification, plays an important role in the development of cardiac fibrosis by adding acetyl groups to lysine residues. Many acetyltransferases and deacetylases regulate the dynamic alterations of acetylation in cardiac fibrosis, regulating a range of pathogenic conditions including oxidative stress, mitochondrial dysfunction, and energy metabolism disturbance. In this review, we demonstrate the critical roles that acetylation modifications caused by different types of pathological injury play in cardiac fibrosis. Furthermore, we propose therapeutic acetylation-targeting strategies for the prevention and treatment of patients with cardiac fibrosis.

Abstract In this study, aged biochar (CCB350 and CCB650) were obtained from pyrolysis of corn stalk biochar (CB350 and CB650) at the degree of 350 °C and 650 °C by artificial oxidation with hydrogen peroxide (H2O2). Also, the mechanism of Pb2+ and Cd2+ on fresh and aged biochars was analyzed qualitatively and quantitatively by batch adsorption experiments combined with characterization. The adsorption isotherm results showed that aging treatment decreased the adsorption capacity of Pb2+ and Cd2+ and inhibited the competitive adsorption behavior of heavy metals. In the single-metal system, precipitation and cation exchange were considered as the main adsorption mechanisms for CB350 and CB650, with a ratio of 40.07–48.23% and 38.04–57.19%, respectively. Competition between Pb2+ and Cd2+ increased the relative contribution of mineral precipitation, but decreased the contribution of cation exchange mechanism. Aging resulted in the rise of the contribution of surface complexation to the adsorption of Pb2+ and Cd2+ on biochars, especially in low-temperature biochars, but weakened the contribution of mineral precipitation to the adsorption. Further, the contribution of other adsorption mechanisms was significantly enhanced for high-temperature aged biochars. These results are important to evaluate its long-term application prospects in the natural environment.

Since the first Immune Checkpoint Inhibitor was developed, tumor immunotherapy has entered a new era, and the response rate and survival rate of many cancers have also been improved. Despite the success of immune checkpoint inhibitors, resistance limits the number of patients who can achieve a lasting response, and immune-related adverse events complicate treatment. The mechanism of immune-related adverse events (irAEs) is unclear. We summarize and discuss the mechanisms of action of immune checkpoint inhibitors, the different types of immune-related adverse events and their possible mechanisms, and describe possible strategies and targets for prevention and therapeutic interventions to mitigate them.

Liver cancer is a common malignancy with high morbidity and mortality rates. Changes in liver metabolism are key factors in the development of primary hepatic carcinoma, and mitochondrial dysfunction is closely related to the occurrence and development of tumours. Accordingly, the study of the metabolic mechanism of mitochondria in primary hepatic carcinomas has gained increasing attention. A growing body of research suggests that defects in mitochondrial respiration are not generally responsible for aerobic glycolysis, nor are they typically selected during tumour evolution. Conversely, the dysfunction of mitochondrial oxidative phosphorylation (OXPHOS) may promote the proliferation, metastasis, and invasion of primary hepatic carcinoma. This review presents the current paradigm of the roles of aerobic glycolysis and OXPHOS in the occurrence and development of hepatocellular carcinoma (HCC). Mitochondrial OXPHOS and cytoplasmic glycolysis cooperate to maintain the energy balance in HCC cells. Our study provides evidence for the targeting of mitochondrial metabolism as a potential therapy for HCC.

Crop type mapping is an indispensable topic in the agricultural field and plays an important role in agricultural intelligence. In crop type mapping, most studies focus on time series models. However, in our experimental area, the images of the crop harvest stage can be obtained from single temporal remote sensing images. Only using single temporal data for crop type mapping can reduce the difficulty of dataset production. In addition, the model of single temporal crop type mapping can also extract the spatial features of crops more effectively. In this work, we linked crop type mapping with 2D semantic segmentation and designed CACPU-Net based on single-source and single-temporal autumn Sentinel-2 satellite images. First, we used a shallow convolutional neural network, U-Net, and introduced channel attention mechanism to improve the model’s ability to extract spectral features. Second, we presented the Dice to compute loss together with cross-entropy to mitigate the effects of crop class imbalance. In addition, we designed the CP module to additionally focus on hard-to-classify pixels. Our experiment was conducted on BeiDaHuang YouYi of Heilongjiang Province, which mainly grows rice, corn, soybean, and other economic crops. On the dataset we collected, through the 10-fold cross-validation experiment under the 8:1:1 dataset splitting scheme, our method achieved 93.74% overall accuracy, higher than state-of-the-art models. Compared with the previous model, our improved model has higher classification accuracy on the parcel boundary. This study provides an effective end-to-end method and a new research idea for crop type mapping. The code and the trained model are available on https://github.com/mooneed/CACPU-Net.

BackgroundChemoresistance generally develops in patients with advanced epithelial ovarian cancer, and the prognosis is still very poor, with an expected survival time of less than one year. For this population of individuals, there is currently no standard protocol for clinical benefit.Case presentationWe report a case of an elderly woman diagnosed with stage IIIC high-grade serous ovarian cancer (HGSOC). During a follow-up time of 6 years, the patient initially received multiple sequential courses of chemotherapy with platinum-based regimens and with no maintenance therapy. Similar to most patients with advanced HGSOC, she developed platinum resistance and experienced poor treatment results with a short progression-free survival (PFS). Ultimately, we gave the patient traditional non-platinum-based chemotherapy with bevacizumab and high-dose-rate interstitial brachytherapy followed by olaparib as a maintenance therapy. Up to now, the patient did response well to the treatment, and the PFS had exceeded 12 months.ConclusionHigh-dose-rate interstitial brachytherapy combination with PARP inhibitors may be an option for isolated chemoresistant recurrent epithelial ovarian cancer.

Background: In-hospital cardiac arrest (IHCA) is a common clinical event with poor outcomes. Former IHCA registries in China were local, inconsistent in data reporting, and lacked attention to the process of care. Therefore, we designed and implemented the BASeline Investigation of In-hospital Cardiac Arrest (BASIC-IHCA), the first national IHCA registry in China. Methods: BASIC-IHCA is a prospective, multicenter, observational study with a nationwide surveillance network covering urban and rural hospitals from seven geographic regions of China. IHCA patients were enrolled continuously, and data were collected from medical records by investigators at participating hospitals. Key variables referring to the updated Utstein Template included patient information, event variables, process of care, and outcomes. Follow-up was conducted by telephone interview to obtain details on long-term survival and neurological status. Results: Thirty-two urban hospitals and eight rural hospitals from twenty-nine provinces in seven geographic regions of China participated in BASIC-IHCA. The starting time of enrollment ranged from July 1, 2019, to January 1, 2020. By December 31, 2020, 35,451 IHCAs were enrolled in all participating hospitals, of which 19,493 (55%) received CPR, with a predominance of males (65%) and a median age of 65 years. Conclusion: BASIC-IHCA is the first national registry for IHCA in China. It will describe the epidemiology and outcomes of IHCA from a nationwide perspective, with a particular focus on details of the process of care for quality improvement. Meanwhile, it will help to facilitate the standardization of IHCA-related data reporting in China.

This paper explores the joint cache placement and 3D deployment of Unmanned Aerial Vehicle (UAV) groups, utilizing potential game theory and a two-hop UAV cooperative caching mechanism, which could create a tradeoff between latency and coverage. The proposed scheme consists of three parts: first, the initial 2D location of UAV groups is determined through K-means, with the optimal altitude based on the UAV coverage radius. Second, to balance the transmission delay and coverage, the MOS (Mean Opinion Score) and coverage are designed to evaluate the performance of UAV-assisted networks. Then, the potential game is modeled, which transfers the optimization problem into the maximization of the whole network utility. The locally coupling effect resulting from action changes among UAVs is considered in the design of the potential game utility function. Moreover, a log-linear learning scheme is applied to solve the problem. Finally, the simulation results verify the superiority of the proposed scheme in terms of the achievable transmission delay and coverage performance compared with two other tested schemes. The coverage ratio is close to 100% when the UAV number is 25, and the user number is 150; in addition, this game outperforms the benchmarks when it comes to maximizing MOS of users.

Using adaptive dynamic programming (ADP), this paper presents a novel attitude-tracking scheme for over-actuated tailless unmanned aerial vehicles (UAVs) that integrates control and control allocation while accounting for nonlinearity and nonaffine control inputs. The proposed method uses the idea of nonlinear dynamic inversion to create an augmented system and converts the optimal tracking problem into an optimal regulation problem using a discounted performance function. Drawing inspiration from incremental control, this method achieves optimal tracking control for the nonaffine system by simply using a critic-only structure. Moreover, the unique design of the performance function ensures robustness against model uncertainties and external disturbances. The ADP method was found to outperform traditional control architectures that separate control and control allocation, achieving the same level of attitude-tracking performance through a more optimized approach. Furthermore, unlike many recent optimal controllers for nonaffine systems, our method does not require any model identifiers and demonstrates robustness. The superiority of the ADP-based approach is verified through two simulated scenarios, and its internal mechanism is further discussed. The theoretical analysis of robustness and stability is also provided.

In this single-arm clinical trial, the authors show that treatment of COVID-19 patients with bevacizumab, an anti-vascular endothelial growth factor drug, can improve PaO2/FiO2 ratios and oxygen-support status. Relative to an external control group, bevacizumab shows clinical efficacy by improving oxygenation.

Abstract Background The Global Trigger Tool (GTT),which is a method using “triggers” to review medical record retrospectively to identify possible adverse events. Several studies showed that the GTT was effective. However, there were only a few localized trigger tools that had been established to detect pediatric adverse drug events (ADEs) in China. This study aimed to establish a pediatric trigger tool based on GTT, to examine the performance by detecting pediatric inpatients ADEs in a Chinese hospital (a retrospective review), and to investigate the factors associating with the occurrence of ADEs. Methods The triggers were established by three steps including literature search, triggers extraction and revision, and experts investigation. A retrospective cohort study was conducted to detect ADEs by using 200 pediatric inpatient records of Sichuan Provincial People’s Hospital. Results Thirty-three preliminary triggers were established, and 2 rounds of experts investigation were conducted. Finally, 33 triggers were established. In the retrospective review, the positive trigger rate was 64.0%, while the positive predictive value (PPV) was 24.9%. The occurrence of inpatients with ADEs was 20.5%. ADEs/100 admissions were 49.0. ADEs/1000 patient days were 46.89. The most common ADE categories were leukocyte disorders, skin disorders and platelet disorders. The severity of 39 ADEs was grade 1, 55 ADEs was grade 2, 4 ADEs was grade 3. The highest frequency of ADE-related drugs was antineoplastic, followed by antibacterial. The length of stay and the leukemia in the diagnosed diseases were positively correlated with ADEs. Conclusions The 33 pediatric triggers may detect ADEs effectively, but still need to be optimized. This study may provide some references for further research in order to improve the rationality and safety of medication.

Background To investigate the diagnostic efficacy of long noncoding RNA metastasis‐associated in lung adenocarcinoma transcript l (MALAT1) as a candidate serological biomarker for non‐small cell lung cancer (NSCLC). Methods Diagnostic studies relevant to circulation long noncoding RNA MALAT1 as a candidate serological biomarker for NSCLC were electronically systematically searched in PubMed, EMBASE, EBSCO and CNKI databases. Suitable studies were included in the meta‐analysis by pooling the diagnostic sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (−LR), diagnostic odds ratio (DOR) and area under the symmetric ROC curve (AUC) through a random or fixed effects model. Deeks' funnel plot was applied for publication bias evaluation. Results Six studies with eight datasets were finally included in the meta‐analysis after a systematic search of the databases was performed. The pooled diagnostic sensitivity, specificity, +LR, −LR and DOR were 0.81 (95% CI:0.78–0.84), 0.67 (95% CI:0.63–0.71), 2.61 (95% CI:1.81–3.71), 0.28 (95% CI:0.19–0.43) and 13.73 (95% CI:6.19–30.44), respectively. The pooled area under the ROC curve (AUC) were 0.8663 and 0.8658, respectively by symmetric and asymmetric methods. Conclusion Based on the results of our study, serum long noncoding RNA MALAT1 is a promising biomarker for NSCLC screening. However, due to its low specificity, MALAT1 positive cases need further validation for NSCLC by other diagnostic methods such as radiology, cytology, etc.

Background: Patients with acute heart failure (AHF) who require continuous renal replacement therapy (CRRT) have a high risk of in-hospital mortality. It is clinically important to screen high-risk patients using a model or scoring system. This study aimed to develop and validate a simple-to-use nomogram consisting of independent prognostic variables for the prediction of in-hospital mortality in patients with AHF undergoing CRRT.Methods: We collected clinical data for 121 patients with a diagnosis of AHF who underwent CRRT in an AHF unit between September 2011 and August 2020 and from 105 patients in the medical information mart for intensive care III (MIMIC-III) database. The nomogram model was created using a visual processing logistic regression model and verified using the standard method.Results: Patient age, days after admission, lactic acid level, blood glucose concentration, and diastolic blood pressure were the significant prognostic factors in the logistic regression analyses and were included in our model (named D-GLAD) as predictors. The resulting model containing the above-mentioned five factors had good discrimination ability in both the training group (C-index, 0.829) and the validation group (C-index, 0.740). The calibration and clinical effectiveness showed the nomogram to be accurate for the prediction of in-hospital mortality in both the training and validation cohort when compared with other models. The in-hospital mortality rates in the low-risk, moderate-risk, and high-risk groups were 14.46, 40.74, and 71.91%, respectively.Conclusion: The nomogram allowed the optimal prediction of in-hospital mortality in adults with AHF undergoing CRRT. Using this simple-to-use model, the in-hospital mortality risk can be determined for an individual patient and could be useful for the early identification of high-risk patients. An online version of the D-GLAD model can be accessed at https://ahfcrrt-d-glad.shinyapps.io/DynNomapp/.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT0751838.

Background: The best anticoagulation choice for patients undergoing transcatheter aortic valve replacement (TAVR) with indications of oral anticoagulation (OAC) remains uncertain. We carried out a comprehensive analysis adopting updated evidence that investigated the efficacy and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in this population. Methods: A systematic search has been conducted through PubMed, Embase, and Cochrane Library to collect randomized controlled trials (RCTs) and real-world studies comparing the therapy outcomes of DOACs with VKAs in patients undergoing TAVR with indications of OAC up to Dec 2021. Included studies reported all-cause mortality, bleeding, stroke, or composite endpoint. A random-effects model was used and followed a sensitivity analysis based on the heterogeneity. In addition, five scenario analyses were performed to robust our findings. Results: Our analysis included 11 articles enrolling a total of 8934 patients undergone TAVR with indications of OAC (DOACs group = 3890, VKAs group = 5044). Pooled analysis revealed no significant different risk of all-cause mortality (aHR: 0.95, 95% CI: 0.65–1.39, I2: 90.6%), stroke (aHR: 0.86, 95% CI: 0.55–1.35, I2: 44.3%), bleeding (aHR: 0.83, 95% CI: 0.61–1.13, I2: 76.3%), and composite endpoint (aHR: 1.05, 95% CI: 0.88–1.24, I2: 11.7%) in the DOACs and VKAs groups. Various forms of death, stroke and bleeding, including cardiovascular death (aHR: 0.92, 95% CI: 0.64–1.33, I2: 34.1%), hemorrhagic stroke (aHR: 0.63, 95% CI: 0.23–1.75, I2: 22.7%), ischemic stroke (aHR: 0.79, 95% CI: 0.56–1.15, I2: 0.0%), transient ischemic attack (aHR: 0.75, 95% CI: 0.40–1.41, I2: 0.0%), major or life-threatening bleeding (aHR: 0.96, 95% CI: 0.74–1.24, I2: 27.9%), and minor bleeding (aHR: 0.90, 95% CI: 0.52–1.57, I2: 54.3%), also showed similar rates among DOACs and VKAs groups. The results based on five scenarios confirmed the said findings. Conclusions: Compared with VKAs, the efficacy and safety of DOACs were comparable for treating TAVR patients combined with anticoagulation indications. Further large-scale RCTs investigating more detailed scenarios are still needed to confirm the optimal anticoagulation strategy.

ObjectiveThe prognosis of patients with breast cancer liver metastasis (BCLM) was poor. We aimed at constructing a nomogram to predict overall survival (OS) for BCLM patients using the SEER (Surveillance Epidemiology and End Results) database, thus choosing an optimized therapeutic regimen to treat.MethodsWe identified 1173 patients with BCLM from the SEER database and randomly divided them into training (n=824) and testing (n=349) cohorts. The Cox proportional hazards model was applied to identify independent prognostic factors for BCLM, based on which a nomogram was constructed to predict 1-, 2-, and 3-year OS. Its discrimination and calibration were evaluated by the Concordance index (C-index) and calibration plots, while the accuracy and benefits were assessed by comparing it to AJCC-TNM staging system using the decision curve analysis (DCA). Kaplan-Meier survival analyses were applied to test the clinical utility of the risk stratification system.ResultsGrade, marital status, surgery, radiation therapy, chemotherapy, CS tumor size, tumor subtypes, bone metastatic, brain metastatic, and lung metastatic were identified to be independent prognostic factors of OS. In comparison with the AJCC-TNM staging system, an improved C-index was obtained (training group: 0.701 vs. 0.557, validation group: 0.634 vs. 0.557). The calibration curves were consistent between nomogram-predicted survival probability and actual survival probability. Additionally, the DCA curves yielded larger net benefits than the AJCC-TNM staging system. Finally, the risk stratification system can significantly distinguish the ones with different survival risk based on the different molecular subtypes.ConclusionWe have successfully built an effective nomogram and risk stratification system to predict OS in BCLM patients, which can assist clinicians in choosing the appropriate treatment strategies for individual BCLM patients.

α-Glycosidase inhibitors could inhibit the digestion of carbohydrates into glucose and promote glucose conversion, which have been used for the treatment of type 2 diabetes. In the present study, 52 candidates of α-glycosidase inhibitors were selected from commercial Specs compound library based on molecular docking–based virtual screening. Four different scaffold compounds (7, 22, 37, and 44) were identified as α-glycosidase inhibitors with IC50 values ranging from 9.99 to 35.19 μM. All these four compounds exerted better inhibitory activities than the positive control (1-deoxynojirimycin, IC50 = 52.02 μM). The fluorescence quenching study and kinetic analysis revealed that all these compounds directly bind to α-glycosidase and belonged to the noncompetitive α-glycosidase inhibitors. Then, the binding modes of these four compounds were carefully investigated. Significantly, these four compounds showed nontoxicity (IC50 > 100 μM) toward the human normal hepatocyte cell line (LO2), which indicated the potential of developing into novel candidates for type 2 diabetes treatment.

Evidence has shown that long non-coding RNAs (lncRNA) play pivotal roles in cancer promotion as well as suppression. But the molecular mechanism of lncRNA TMPO antisense transcript 1 (TMPO-AS1) in lung cancer (LC) remains unclear. This study mainly investigated the effect of TMPO-AS1 in LC treatment. TMPO-AS1 was tested by Kaplan-Meier method. Quantitative real time polymerase chain reaction (qRT-PCR) was employed to assess the expressions of TMPO-AS1, miR-143-3p, and CDK1 respectively in LC tissues and cell lines. TMPO-AS1, miR-143-3p and CDK1 expressions in LC cells were regulated through cell transfection, followed by MTT for cell viability detection. Besides, dual-luciferase reporter assays were performed to verify the interrelated microRNA of TMPO-AS1 and the target of miR-143-3p. Western blot experiments were used to examine the expressions of apoptosis-related proteins, and flow cytometry tested the cell apoptosis in treated cells. TMPO-AS1 and CDK1 were overexpressed in LC tissues and cells, while miR-143-3p level was suppressed. The decrease of TMPO-AS1 led to the increase of miR-143-3p, which further resulted in the reduction of CDK1. Down-regulating TMPO-AS1 reduced LC cell viability, motivated cell apoptosis, as well as promoted the expressions of Bcl and CCND1 and restrained Caspase-3 level, but all these consequences were abrogated by miR-143-3p inhibitor. Simultaneously, siCDK1 could reverse the anti-apoptosis and pro-activity functions of miR-143-3p inhibitor in LC cells. Down-regulation of TMPO-AS1 has the effects of pro-apoptosis in LC by manipulating miR-143-3p/CDK1, which is hopeful to be a novel therapy for LC patients.

Recycled resource and consumer satisfaction drive bicycle enterprises to take effort to recycle damaged bicycles. Considering consumers’ riding experience, this paper analyzes a closed-loop supply chain where the operator sets price and recycling effort, and the supplier determines wholesale price. Rent and recycling strategies in integrated and decentralized channels are analyzed, and four types of revenue and cost-sharing contracts are compared, and the linear transfer payment-CS contract is designed to coordinate the decentralized supply chain. The results show that the consumers’ concern for riding experience can encourage the operator to increase recycling effort and the operator increases the rents and recycling effort over time. Besides, the sharing deposit income among supply chain members only affects the wholesale price and does not change the decisions of rent and recovery effort. In other words, the deposit is used to adjust the profit distribution among members, and there is no difference for consumers and society.

The differences of the basic network flow characteristics between BotCloud and normal cloud services were not obvious, and this led to the inefficiency of the method in BotCloud detection based on network flow characteristics analysis. To solve this problem, a CNN(convolution neural network)-based method for detecting the BotCloud was pro-posed. First, it extracted the basic network flow characteristics from network flow data packets. Second, it mapped the basic network flow characteristics into gray image. Finally, in order to detect BotCloud, it utilized CNN algorithm to learn and extract characteristics that were more abstract to express the hidden model and structural relationship in the network data flow. The experimental results show that the proposed method can not only enhance the accuracy of detec-tion, but also greatly reduce the time required for detecting.

On July 1, 2011, the Chinese government launched a national Action Plan for antibiotic stewardship targeting antibiotic misuse in public hospitals. The aim of this study was to evaluate the impacts of the Action Plan in terms of frequency and intensity of antibiotic utilization and patients costs in public general hospitals.Administrative pharmacy data from July 2010 to June 2014 were sampled from 65 public general hospitals and divided into three segments: (1) July 2010 to June 2011 as the preparation period; (2) July 2011 to June 2012 as the intervention period; and (3) July 2012 to June 2014 as the assessment period. The outcome measures included (1) antibiotic prescribing rates; (2) intensity of antibiotic consumption; (3) patients costs; and (4) duration of peri-operative antibiotic treatment in clean surgeries of thyroidectomy, breast, hernia, and orthopedic procedures. Longitudinal and cross-sectional analyses were conducted.Longitudinal analyses showed significant trend changes in the frequency and intensity of antibiotic consumption, the patients' costs on antibiotics, and the duration of antibiotic treatment received by surgical patients undergoing the 4 clean procedures during the intervention period. Cross-sectional analyses showed that the antibiotic prescribing rates were reduced to 35.3% and 12.9% in inpatient and outpatient settings, that the intensity of antibiotic consumption was reduced to 35.9 DDD/100 bed-days, that patients' costs on antibiotics were reduced significantly, and that the duration of peri-operative antibiotic treatment received by surgical patients undergoing the 4 types of clean procedures decreased to less than 24 hour during the assessment period.The Action Plan, as a combination of managerial and professional strategies, was effective in reducing the frequency and intensity of antibiotic consumption, patients' costs on antibiotics, and the duration of peri-operative antibiotic treatment in the 4 clean surgeries.

With the proportion of air conditioners increasing gradually, they can provide a certain amount of frequency-controlled reserves for a micro-grid. Optimizing utilization of air conditioners and considering load response characteristics and customer comfort, the frequency adjustment model is a quadratic function model between the trigger temperature of the air conditioner compressor, and frequency variation is provided, which can be used to regulate the trigger temperature of the air conditioner when the micro-grid frequency rises and falls. This frequency adjustment model combines a primary frequency modulation method and a secondary frequency modulation method of the energy storage system, in order to optimize the frequency of a micro-grid. The simulation results show that the frequency modulation strategy for air conditioners can effectively improve the frequency modulation ability of air conditioners and frequency modulation effects of a micro-grid in coordination with an energy storage system.

The main objective of this paper is to investigate the pharmacokinetics of NM394 (an active metabolite of prulifloxacin) and evaluate the dose relationship and accumulation characteristics after single and multiple doses of prulifloxacin. Thirty healthy volunteers were given 132 mg, 264 mg, and 528 mg of prulifloxacin capsules in a randomized test corresponding to low, medium and high groups for single dose trial. With one-week washout period, 264 mg of prulifloxacin capsules were given to eight volunteers of the medium group for multiple doses trial. The concentration of NM394 in serum was determined by a sensitive HPLC method and its pharmacokinetic parameters were analyzed by DAS2.0.1 and evaluated by SPSS statistic software (version 13.0). Various parameters were determined. Numerical experiments show that the pharmacokinetic parameters of NM394 displayed first order linear pharmacokinetic character. There are no big differences in pharmacokinetic characteristics of NM394 between single and multiple doses. Almost no significant accumulation of drugs is observed after multiple doses of 264 mg per day for 7 d and chronopharmacokinetics were first observed.

OBJECTIVE: Comparing the effects of extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) on outcomes in patients with in-hospital cardiac arrest (IHCA) in China. The benefits of ECPR over CCPR in patients with IHCA remain controversial. DESIGN: This article analyzed data from the BASeline Investigation of In-hospital Cardiac Arrest (BASIC-IHCA) study, which consecutively enrolled patients with IHCA from July 1, 2019, to December 31, 2020. Patients who received ECPR were selected as the case group and matched with patients who received CCPR as the control group by propensity score at a ratio of 1:4. A parallel questionnaire survey of participating hospitals was conducted, to collect data on ECPR cases from January 1, 2021 to November 30, 2021. The primary outcome was survival to discharge or 30-day survival. SETTING: We included 39 hospitals across 31 provinces in China. PATIENTS: Patients receiving cardiopulmonary resuscitation and without contraindications to ECPR were selected from the BASIC-IHCA database. Patients older than 75 years, not witnessed, or with cardiopulmonary resuscitation duration less than 10 min were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 4853 patients met the inclusion criteria before matching, with 34 undergoing ECPR (median age, 56.5 yr; 67.65% male) and 4819 underwent CCPR (median age, 59 yr; 64.52% male). There were 132 patients receiving CCPR and 33 patients receiving ECPR who were eventually matched. The ECPR group had significantly higher survival rates at discharge or 30-day survival (21.21% vs. 7.58%, p = 0.048). The ECPR group had significantly lower mortality rates (hazard ratio 0.57; 95% CI, 0.38-0.91) than the CCPR group at discharge or 30 days. Besides the BASIC-IHCA study, the volume of ECPR implementations and the survival rate of patients with ECPR (29.4% vs. 10.4%. p = 0.004) in participating hospitals significantly improved. CONCLUSIONS: ECPR may be beneficial compared with CCPR for patient survival after IHCA and should be considered for eligible patients with IHCA. [ABSTRACT FROM AUTHOR]