Relationship Between Family History and Quality of Life in Patients with Psoriasis: A Cross-Sectional Study from China.

Purpose: The purpose of this study was to investigate the comprehensive impact of family history of psoriasis, lesion size, disease severity, and the possibility of joint involvement on patients' quality of life(QoL). Patients and Methods: Data from 5961 patients with psoriasis recruited from 440 hospitals throughout China were analyzed. The effects of family history of psoriasis, Body Surface Area(BSA), Psoriasis Area and Severity Index(PASI), and Psoriasis Epidemiology Screening Tool(PEST) on their Dermatology Life Quality Index(DLQI) were studied using a moderated chained mediated effects test. Results: A total of 912 patients (15.30%) had a family history of psoriasis, and 5071 patients (85.10%) had plaque psoriasis. In patients with plaque psoriasis, the variables of family history, PASI, PEST, and DLQI were positively correlated with each other. Additionally, in patients with other types of psoriasis, PASI was positively correlated with PEST and DLQI. Age was positively correlated with PASI and PEST and negatively correlated with DLQI in patients with plaque psoriasis; their Body Mass Index(BMI) and disease duration were in positive correlation with PASI and PEST. The mediation effect of PASI and PEST between family history and DLQI was remarkable in patients with plaque psoriasis and not in those with other types of psoriasis. BSA moderated the association between family history and PASI in patients with plaque psoriasis. Conclusion: PASI and PEST play a chain mediating role in the relationship between family history and DLQI in patients with plaque psoriasis, and high levels of BSA increase the ability of family history to positively predict PASI in plaque psoriasis, thereby affecting the patient's QoL.

Discovery of Antifungal Norsesquiterpenoids from a Soil-Derived Streptomyces microflavus: Targeting Biofilm Formation and Synergistic Combination with Amphotericin B against Yeast-like Fungi.

Thirty-five norsesquiterpenoids were isolated from the fermentation broth of Streptomyces microflavus from the forest soil of Ailaoshan in China. The structures of new compounds (1-5, 10-26) were elucidated by comprehensive spectroscopic analysis including data from experimental and calculated ECD spectra, as well as Mosher's reagent derivatives method. Norsesquiterpenoids showed different levels of antifungal activity with MIC80 values ranging from 25 to 200 µg/mL against Candida albicans, Candida parapsilosis, and Cryptococcus neoformans. The combining isolated norsesquiterpenoids with amphotericin B resulted in a synergistic interaction against test yeast-like fungi with a fractional inhibitory concentration index < 0.5. Compound 33 significantly inhibited biofilm formation and destroyed the preformed biofilm of fungi. Moreover, 33 downregulated the expression of adhesion-related genes HWP1, ALS1, ALS3, ECE1, EAP1, and BCR1 to inhibit the adhesion of C. albicans. Findings from the current study highlight the potential usage of norsesquiterpenoids from soil-derived Streptomyces for antifungal leads discovery.

Efficacy and safety of perioperative therapy for locally resectable gastric cancer: A network meta-analysis of randomized clinical trials.

BACKGROUND: Gastric cancer (GC) is the fifth most commonly diagnosed malignancy worldwide, with over 1 million new cases per year, and the third leading cause of cancer-related death. AIM: To determine the optimal perioperative treatment regimen for patients with locally resectable GC. METHODS: A comprehensive literature search was conducted, focusing on phase II/III randomized controlled trials (RCTs) assessing perioperative chemotherapy and chemoradiotherapy in treating locally resectable GC. The R0 resection rate, overall survival (OS), disease-free survival (DFS), and incidence of grade 3 or higher nonsurgical severe adverse events (SAEs) associated with various perioperative regimens were analyzed. A Bayesian network meta-analysis was performed to compare treatment regimens and rank their efficacy. RESULTS: Thirty RCTs involving 8346 patients were included in this study. Neoadjuvant XELOX plus neoadjuvant radiotherapy and neoadjuvant CF were found to significantly improve the R0 resection rate compared with surgery alone, and the former had the highest probability of being the most effective option in this context. Neoadjuvant plus adjuvant FLOT was associated with the highest probability of being the best regimen for improving OS. Owing to limited data, no definitive ranking could be determined for DFS. Considering nonsurgical SAEs, FLO has emerged as the safest treatment regimen. CONCLUSION: This study provides valuable insights for clinicians when selecting perioperative treatment regimens for patients with locally resectable GC. Further studies are required to validate these findings.

Elucidating the changes in the heterogeneity and function of radiation-induced cardiac macrophages using single-cell RNA sequencing.

Purpose: A mouse model of irradiation (IR)-induced heart injury was established to investigate the early changes in cardiac function after radiation and the role of cardiac macrophages in this process. Methods: Cardiac function was evaluated by heart-to-tibia ratio, lung-to-heart ratio and echocardiography. Immunofluorescence staining and flow cytometry analysis were used to evaluate the changes of macrophages in the heart. Immune cells from heart tissues were sorted by magnetic beads for single-cell RNA sequencing, and the subsets of macrophages were identified and analyzed. Trajectory analysis was used to explore the differentiation relationship of each macrophage subset. The differentially expressed genes (DEGs) were compared, and the related enriched pathways were identified. Single-cell regulatory network inference and clustering (SCENIC) analysis was performed to identify the potential transcription factors (TFs) which participated in this process. Results: Cardiac function temporarily decreased on Day 7 and returned to normal level on Day 35, accompanied by macrophages decreased and increased respectively. Then, we identified 7 clusters of macrophages by single-cell RNA sequencing and found two kinds of stage specific macrophages: senescence-associated macrophage (Cdkn1ahighC5ar1high) on Day 7 and interferon-associated macrophage (Ccr2highIsg15high) on Day 35. Moreover, we observed cardiac macrophages polarized over these two-time points based on M1/M2 and CCR2/major histocompatibility complex II (MHCII) expression. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses suggested that macrophages on Day 7 were characterized by an inflammatory senescent phenotype with enhanced chemotaxis and inflammatory factors, while macrophages on Day 35 showed enhanced phagocytosis with reduced inflammation, which was associated with interferon-related pathways. SCENIC analysis showed AP-1 family members were associated with IR-induced macrophages changes. Conclusion: We are the first study to characterize the diversity, features, and evolution of macrophages during the early stages in an IR-induced cardiac injury animal model.

Overexpression of Rhodiola crenulata glutathione peroxidase 5 increases cold tolerance and enhances the pharmaceutical value of the hairy roots.

Rhodiola crenulata, a plant of great medicinal value found in cold high-altitude regions, has been excessively exploited due to the difficulty in cultivation. Understanding Rhodiola crenulata's adaptation mechanisms to cold environment can provide a theoretical basis for artificial breeding. Glutathione peroxidases (GPXs), critical enzymes found in plants, play essential roles in antioxidant defense through the ascorbate-glutathione cycle. However, it is unknown whether GPX5 contributes to Rhodiola crenulata's cold tolerance. In this study, we investigated the role of GPX5 in Rhodiola crenulata's cold tolerance mechanisms. By overexpressing Rhodiola crenulata GPX5 (RcGPX5) in yeast and Arabidopsis thaliana, we observed down-regulation of Arabidopsis thaliana GPX5 (AtGPX5) and increased cold tolerance in both organisms. Furthermore, the levels of antioxidants and enzyme activities in the ascorbate-glutathione cycle were elevated, and cold-responsive genes such as AtCBFs and AtCORs were induced. Additionally, RcGPX5 overexpressing lines showed insensitivity to exogenous abscisic acid (ABA), suggesting a negative regulation of the ABA pathway by RcGPX5. RcGPX5 also promoted the expression of several thioredoxin genes in Arabidopsis and interacted with two endogenous genes of Rhodiola crenulata, RcTrx2-3 and RcTrxo1, located in mitochondria and chloroplasts. These findings suggest a significantly different model in Rhodiola crenulata compared to Arabidopsis thaliana, highlighting a complex network involving the function of RcGPX5. Moreover, overexpressing RcGPX5 in Rhodiola crenulata hairy roots positively influenced the salidroside synthesis pathway, enhancing its pharmaceutical value for doxorubicin-induced cardiotoxicity. These results suggested that RcGPX5 might be a key component for Rhodiola crenulata to adapt to cold stress and overexpressing RcGPX5 could enhance the pharmaceutical value of the hairy roots.

Exploring the Impact of High-Quality Nursing on Nursing Efficiency and Stress Levels through Visual Electrophysiological Detection.

Objective: To assess the influence of high-quality nursing during visual electrophysiology examinations on both nursing outcomes and stress levels. Methods: A total of 80 patients who underwent visual electrophysiology examinations in the hospital from January 2021 to January 2022 were included as study subjects and randomized into two groups using random allocation. This random assignment ensures that each patient has an equal chance of being assigned to either group, minimizing the effects of confounding variables and evenly distributing potential bias. The control group received conventional nursing care, while the study group received quality nursing care, with 40 patients in each group. Patients in both groups were compared regarding nursing impact, occurrence of adverse reactions, pain level, and stress status. Results: In the study group, 39 patients exhibited high levels of cooperation, while 1 demonstrated a low degree of cooperation. Conversely, in the control group, 36 subjects were highly cooperative, but 6 displayed a low degree of cooperation. The cooperation rate was significantly higher in the study group compared to the control group (97.5% vs. 85.0%, χ² = 3.914, P = .048). SAS scores and SDS scores after treatment were observed to be lower in the study group compared to those in the control group (P < .05). The increase in scores within the study group was notably less than that observed in the control group (P < .05). The results indicate that 38 patients in the study group reported satisfaction, while 31 in the control group expressed satisfaction. The nursing satisfaction rate was significantly higher in the study group than in the control group (P < .05). Conclusions: Quality nursing care during visual electrophysiology examinations proves to be highly effective in enhancing patient compliance, fostering a higher rate of patient cooperation, and mitigating patient stress. Furthermore, it contributes to the improvement of patient satisfaction with nursing care, ultimately elevating the overall healthcare relationship.

The role of ABCC10/MRP7 in anti-cancer drug resistance and beyond.

Multidrug resistance protein 7 (MRP7), also known as ATP-binding cassette (ABC) transporter subfamily C10 (ABCC10), is an ABC transporter that was first identified in 2001. ABCC10/MRP7 is a 171 kDa protein located on the basolateral membrane of cells. ABCC10/MRP7 consists of three transmembrane domains and two nucleotide binding domains. It mediates multidrug resistance of tumor cells to a variety of anticancer drugs by increasing drug efflux and results in reducing intracellular drug accumulation. The transport substrates of ABCC10/MRP7 include antineoplastic drugs such as taxanes, vinca alkaloids, and epothilone B, as well as endobiotics such as leukotriene C4 (LTC4) and estradiol 17 ß-D-glucuronide. A variety of ABCC10/MRP7 inhibitors, including cepharanthine, imatinib, erlotinib, tariquidar, and sildenafil, can reverse ABCC10/MRP7-mediated MDR. Additionally, the presence or absence of ABCC10/MRP7 is also closely related to renal tubular dysfunction, obesity, and other diseases. In this review, we discuss: 1) Structure and functions of ABCC10/MRP7; 2) Known substrates and inhibitors of ABCC10/MRP7 and their potential therapeutic applications in cancer; and 3) Role of ABCC10/MRP7 in non-cancerous diseases.

Proton Therapy in Breast Cancer: A Review of Potential Approaches for Patient Selection.

Proton radiotherapy may be a compelling technical option for the treatment of breast cancer due to its unique physical property known as the "Bragg peak." This feature offers distinct advantages, promising superior dose conformity within the tumor area and reduced radiation exposure to surrounding healthy tissues, enhancing the potential for better treatment outcomes. However, proton therapy is accompanied by inherent challenges, primarily higher costs and limited accessibility when compared to well-developed photon irradiation. Thus, in clinical practice, it is important for radiation oncologists to carefully select patients before recommendation of proton therapy to ensure the transformation of dosimetric benefits into tangible clinical benefits. Yet, the optimal indications for proton therapy in breast cancer patients remain uncertain. While there is no widely recognized methodology for patient selection, numerous attempts have been made in this direction. In this review, we intended to present an inspiring summarization and discussion about the current practices and exploration on the approaches of this treatment decision-making process in terms of treatment-related side-effects, tumor control, and cost-efficiency, including the normal tissue complication probability (NTCP) model, the tumor control probability (TCP) model, genomic biomarkers, cost-effectiveness analyses (CEAs), and so on. Additionally, we conducted an evaluation of the eligibility criteria in ongoing randomized controlled trials and analyzed their reference value in patient selection. We evaluated the pros and cons of various potential patient selection approaches and proposed possible directions for further optimization and exploration. In summary, while proton therapy holds significant promise in breast cancer treatment, its integration into clinical practice calls for a thoughtful, evidence-driven strategy. By continuously refining the patient selection criteria, we can harness the full potential of proton radiotherapy while ensuring maximum benefit for breast cancer patients.

Therapeutic evolution in HR+/HER2- breast cancer: from targeted therapy to endocrine therapy.

Breast cancer, a complex and varied disease, has four distinct subtypes based on estrogen receptor and human epidermal growth factor receptor 2 (HER2) levels, among which a significant subtype known as HR+/HER2-breast cancer that has spurred numerous research. The prevalence of breast cancer and breast cancer-related death are the most serious threats to women's health worldwide. Current progress in treatment strategies for HR+/HER2-breast cancer encompasses targeted therapy, endocrine therapy, genomic immunotherapy, and supplementing traditional methods like surgical resection and radiotherapy. This review article summarizes the current epidemiology of HR+/HER2-breast cancer, introduces the classification of HR+/HER2-breast cancer and the commonly used treatment methods. The mechanisms of action of various drugs, including targeted therapy drugs and endocrine hormone therapy drugs, and their potential synergistic effects are deeply discussed. In addition, clinical trials of these drugs that have been completed or are still in progress are included.

The greener the living environment, the better the health? Examining the effects of multiple green exposure metrics on physical activity and health among young students.

The sedentary and less active lifestyle of modern college students has a significant impact on the physical and mental well-being of the college community. Campus Green Spaces (GSs) are crucial in promoting physical activity and improving students' health. However, previous research has focused on evaluating campuses as a whole, without considering the diverse spatial scenarios within the campus environment. Accordingly, this study focused on the young people's residential scenario in university and constructed a framework including a comprehensive set of objective and subjective GSs exposure metrics. A systematic, objective exposure assessment framework ranging from 2D (GSs areas), and 2.5D (GSs visibility) to 3D (GSs volume) was innovatively developed using spatial analysis, deep learning technology, and unmanned aerial vehicle (UAV) measurement technology. Subjective exposure metrics incorporated GSs visiting frequency, GSs visiting duration, and GSs perceived quality. Our cross-sectional study was based on 820 university students in Nanjing, China. Subjective measures of GSs exposure, physical activity, and health status were obtained through self-reported questionnaires. The Generalized Linear Model (GLM) was used to evaluate the associations between GSs exposure, physical activity, and perceived health. Physical activity and social cohesion were considered as mediators, and path analysis based on Structural Equation Modeling (SEM) was used to disentangle the mechanisms linking GSs exposure to the health status of college students. We found that (1) 2D indicator suggested significant associations with health in the 100m buffer, and the potential underlying mechanisms were: GSs area → Physical activity → Social cohesion → Physical health → Mental health; GSs area → Physical activity → Social cohesion → Mental health. (2) Subjective GSs exposure indicators were more relevant in illustrating exposure-response relationships than objective ones. This study can clarify the complex nexus and mechanisms between campus GSs, physical activity, and health, and provide a practical reference for health-oriented campus GSs planning.

Efficient bio-remediation of multiple aromatic hydrocarbons using different types of thermotolerant, ring-cleaving dioxygenases derived from Aeribacillus pallidus HB-1.

As toxic contaminants, aromatic compounds are widespread in most environmental matrices, and bioenzymatic catalysis plays a critical role in the degradation of xenobiotics. Here, a thermophillic aromatic hydrocarbon degrader Aeribacillus pallidus HB-1 was found. Bioinformatic analysis of the HB-1 genome revealed two ring-cleaving extradiol dioxygenases (EDOs), among which, EDO-0418 was assigned to a new subfamily of type I.1 EDOs and exhibited a broad substrate specificity, particularly towards biarylic substrate. Both EDOs exhibited optimal activities at elevated temperatures (55 and 65 °C, respectively) and showed remarkable thermostability, pH stability, metal ion resistance and tolerance to chemical reagents. Most importantly, simulated wastewater bioreactor experiments demonstrated efficient and uniform degradation performance of mixed aromatic substrates under harsh environments by the two enzymes combined for potential industrial applications. The unveiling of two thermostable dioxygenases with broad substrate specificities and stress tolerance provides a novel approach for highly efficient environmental bioremediation using composite enzyme systems.

Self-Reinforced PTLG Copolymer with Shish Kebab Structures and a Bionic Surface as Bioimplant Materials for Tissue Engineering Applications.

Green and biodegradable materials with great mechanical properties and biocompatibility will offer new opportunities for next-generation high-performance biological materials. Herein, the novel oriented shish kebab crystals of a novel poly(trimethylene carbonate-lactide-glycolide) (PTLG) vascular stent are first reported to be successfully fabricated through a feasible solid-state drawing process to simultaneously enhance the mechanical performance and biocompatibility. The crystal structure of this self-reinforced vascular stent was transformed from spherulites to a shish kebab crystal, which indicates the mechanical interlocking effect and prevents the lamellae from slipping with a significant improvement of mechanical strength to 333 MPa. Meanwhile, it is different from typical biomedical polymers with smooth surface structures, and the as-obtained PTLG vascular stent exhibits a bionic surface morphology with a parallel micro groove and ridge structure. These ridges and grooves were attributed to the reorganization of cytoskeleton fiber bundles following the direction of blood flow shear stress. The structure and parameters of these morphologies were highly similar to the inner surface of blood vessels of the human, which facilitates cell adhesion growth to improve its proliferation, differentiation, and activity on the surface of PTLG.

Biomechanical evaluation of the novel assembled internal fixed system in C2-C3 anterior cervical discectomy and fusion: a finite element analysis.

BACKGROUND: To analyze and compare the biomechanical characteristics of the new combined cervical fusion device (NCCFD) and the traditional cage-plate construct (CPC) to ascertain its effectiveness in anterior cervical discectomy and fusion (ACDF) using finite element analysis. METHODS: A finite element model of the cervical spine, inclusive of the occipital bone was created and validated. In the ACDF model, either CPC or NCCFD was implanted at the C2-C3 segment of the model. A pure moment of 1.0 Nm combined with a follower load of 50 N was directed onto the superior surfaces of the occipital bone to determine flexion, extension, lateral bending (left and right), and axial rotation (left and right). The range of motion (ROM), stress distribution at the bone-implant interface, and facet joint forces were investigated and compared between CPC and NCCFD systems. RESULT: The results showed that the ROMs of the fused levels in both models were nearly zero, and the motions of the unfused segments were similar. In addition, the maximum displacement exhibited nearly identical values for both models. The maximum stress of NCCFD screws in lateral bending and rotational conditions is significantly higher than that of the CPC, while the NCCFD model's maximum stress remains within an acceptable range. Comparing the maximum fusion stress, it was found that the CPC experiences much lower fusion stress in anterior flexion and extension than the NCCFD, with no significant difference between the two in lateral bending and rotational states. Stress on the cage was mainly concentrated on both sides of the wings. Comparing the maximum IDP in the CPC and NCCFD, it was observed that maximum stresses rise in extension and lateral bending for both models. Lastly, stress distributions of the facet joints were generally similar across the two devices. CONCLUSION: NCCFD not only provides the same level of biomechanical stability as CPC but also avoids postoperative complications associated with uneven force damage to the implant. The device offers a novel surgical alternative for ACDF in C2-C3 level.

Research progress of Paris polyphylla in the treatment of digestive tract cancers.

Cancer has become one of the most important causes of human death. In particular, the 5 year survival rate of patients with digestive tract cancer is low. Although chemotherapy drugs have a certain efficacy, they are highly toxic and prone to chemotherapy resistance. With the advancement of antitumor research, many natural drugs have gradually entered basic clinical research. They have low toxicity, few adverse reactions, and play an important synergistic role in the combined targeted therapy of radiotherapy and chemotherapy. A large number of studies have shown that the active components of Paris polyphylla (PPA), a common natural medicinal plant, can play an antitumor role in a variety of digestive tract cancers. In this paper, the main components of PPA such as polyphyllin, C21 steroids, sterols, and flavonoids, amongst others, are introduced, and the mechanisms of action and research progress of PPA and its active components in the treatment of various digestive tract cancers are reviewed and summarized. The main components of PPA have been thoroughly explored to provide more detailed references and innovative ideas for the further development and utilization of similar natural antitumor drugs.

Efficacy of Fire-Needle Therapy in Improving Neurological Function Following Cerebral Infarction and Its Effect on Intestinal Flora Metabolites.

Objective: This study was to investigate the mechanism of action and clinical efficacy of fire-needle therapy in improving neurological function in patients with acute cerebral infarction (identified as a wind-phlegm-blood stasis syndrome in traditional Chinese medicine). Methods: We included patients diagnosed with acute cerebral infarction (wind-phlegm-blood stasis syndrome) admitted to the Encephalopathy and Acupuncture Center of the Second Affiliated Hospital of Tianjin University of Chinese Medicine. We randomly allocated them into the treatment and control groups, with 45 cases in each group. Acupuncture treatments that focused on regulating the mind and dredging the collaterals were used in the control group, while the treatment group additionally received fire-needle therapy. Our indicators included the National Institutes of Health Stroke Scale (NIHSS) scores, the Fugl-Meyer Assessment (FMA) scale, peripheral blood tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), hypersensitivity C-reactive protein (hs-CRP), and intestinal metabolites short-chain fatty acids (SCFAs). We measured these indicators before treatment and 14 days after treatment. Results: The post-treatment NIHSS scores of the two groups were significantly reduced (P < 0.05), and the treatment group showed a more significant decline in the score when compared to the control group (P < 0.05). The treatment group showing significant improvement in the domains of reflex activity, mobility, cooperative movement, and finger movement (P < 0.05). Both groups showed a significant decrease in the IL-17 and hs-CRP levels (P < 0.05), with the treatment group demonstrating a significant declining trend when compared to the control group (P < 0.05). The levels of acetic acid, propionic acid, butyric acid, and valeric acid all increased significantly in the two groups (P < 0.05), with acetic acid and butyric acid increasing significantly in the treatment group when compared to the control group (P < 0.05). Clinical efficacy rate: 78.6% of patients in the treatment group had an excellent rate, whereas it was 30.0% in the control group, and the difference was statistically significant (P < 0.001). Conclusion: Fire-needle therapy was effective in upregulating the SCFA content in patients with acute cerebral infarction (wind-phlegm-blood stasis syndrome), inhibiting the level of the inflammatory response, and improving the recovery of neurological functions. Clinical registration number: Registration website link: https://www.chictr.org.cn. Registration date: 2022/9/27. Registration number: ChiCTR2200064122.

The Effect of Angiotensin Receptor Blockers on In-Stent Restenosis After Stent Implantation: A Meta-Analysis.

AIM: Angiotensin receptor blockers (ARBs) have been shown to inhibit restenosis in vitro and in vivo, but the evidence found in humans is inconsistent. This study aimed to evaluate the effectiveness of ARBs in preventing in-stent restenosis after percutaneous coronary intervention (PCI). METHOD: Databases including the Cochrane Library, MEDLINE, Web of Science, EMBASE, and CNKI were searched to collect randomised controlled trials on ARBs inhibiting restenosis that were published before October 2022. A total of 1,056 patients enrolled in eight trials were included in the study. RESULTS: The ARBs group showed lower target lesion revascularisation than the control group (RR 0.54; 95% CI 0.34-0.86; p=0.01), but the restenosis incidence between these two groups was not statistically significant (RR 0.85; 95% CI 0.65-1.11; p>0.05). CONCLUSION: This study found that ARBs might have a potential effect on reducing target lesion revascularisation after PCI in coronary heart disease patients but has no impact on angiographic restenosis.

Effect of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction: a meta-analysis.

Heart failure is the final stage of several cardiovascular diseases, and the key to effectively treating heart failure is to reverse or delay ventricular remodelling. Levosimendan is a novel inotropic and vasodilator agent used in heart failure, whereas the impact of levosimendan on ventricular remodelling is still unclear. This study aims to investigate the impact of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction. Electronic databases were searched to identify eligible studies. A total of 66 randomized controlled trials involving 7968 patients were included. Meta-analysis results showed that levosimendan increased left ventricular ejection fraction [mean difference (MD) = 3.62, 95% confidence interval (CI) (2.88, 4.35), P < 0.00001] and stroke volume [MD = 6.59, 95% CI (3.22, 9.96), P = 0.0001] and significantly reduced left ventricular end-systolic volume [standard mean difference (SMD) = -0.52, 95% CI (-0.67, -0.37), P < 0.00001], left ventricular end-diastolic volume index [SMD = -1.24, 95% CI (-1.61, -0.86), P < 0.00001], and left ventricular end-systolic volume index [SMD = -1.06, 95% CI (-1.43, -0.70), P < 0.00001]. In terms of biomarkers, levosimendan significantly reduced the level of brain natriuretic peptide [SMD = -1.08, 95% CI (-1.60, -0.56), P < 0.0001], N-terminal pro-brain natriuretic peptide [SMD = -0.99, 95% CI (-1.41, -0.56), P < 0.00001], and interleukin-6 [SMD = -0.61, 95% CI (-0.86, -0.35), P < 0.00001]. Meanwhile, levosimendan may increase the incidence of hypotension [risk ratio (RR) = 1.24, 95% CI (1.12, 1.39), P < 0.0001], hypokalaemia [RR = 1.57, 95% CI (1.08, 2.28), P = 0.02], headache [RR = 1.89, 95% CI (1.50, 2.39), P < 0.00001], atrial fibrillation [RR = 1.31, 95% CI (1.12, 1.52), P = 0.0005], and premature ventricular complexes [RR = 1.86, 95% CI (1.27, 2.72), P = 0.001]. In addition, levosimendan reduced all-cause mortality [RR = 0.83, 95% CI (0.74, 0.94), P = 0.002]. In conclusion, our study found that levosimendan might reverse ventricular remodelling when applied in patients with left ventricular systolic dysfunction, especially in patients undergoing cardiac surgery, decompensated heart failure, and septic shock.

A planar tracking strategy based on multiple-interpretable improved PPO algorithm with few-shot technique.

Facing to a planar tracking problem, a multiple-interpretable improved Proximal Policy Optimization (PPO) algorithm with few-shot technique is proposed, namely F-GBQ-PPO. Compared with the normal PPO, the main improvements of F-GBQ-PPO are to increase the interpretability, and reduce the consumption for real interaction samples. Considering to increase incomprehensibility of a tracking policy, three levels of interpretabilities has been studied, including the perceptual, logical and mathematical interpretabilities. Detailly speaking, it is realized through introducing a guided policy based on Apollonius circle, a hybrid exploration policy based on biological motions, and the update of external parameters based on quantum genetic algorithm. Besides, to deal with the potential lack of real interaction samples in real applications, a few-shot technique is contained in the algorithm, which mainly generate fake samples through a multi-dimension Gaussian process. By mixing fake samples with real ones in a certain proportion, the demand for real samples can be reduced.

A safety screening platform for individualized cardiotoxicity assessment.

Cardiotoxicity remains a major cause of drug withdrawal, partially due to lacking predictability of animal models. Additionally, risk of cardiotoxicity following treatment of cancer patients is treatment limiting. It is unclear which patients will develop heart failure following therapy. Human pluripotent stem cell (hPSC)-derived cardiomyocytes present an unlimited cell source and may offer individualized solutions to this problem. We developed a platform to predict molecular and functional aspects of cardiotoxicity. Our platform can discriminate between the different cardiotoxic mechanisms of existing and novel anthracyclines Doxorubicin, Aclarubicin, and Amrubicin. Doxorubicin and Aclarubicin unlike Amrubicin substantially affected the transcriptome, mitochondrial membrane integrity, contractile force and transcription factor availability. Cardiomyocytes recovered fully within two or three weeks, corresponding to the intermittent clinical treatment regimen. Our system permits the study of hPSC-cardiomyocyte recovery and the effects of accumulated dose after multiple dosing, allowing individualized cardiotoxicity evaluation, which effects millions of cancer patients treated annually.

The role of ferroptosis in cardio-oncology.

With the rapid development of new generations of antitumor therapies, the average survival time of cancer patients is expected to be continuously prolonged. However, these therapies often lead to cardiotoxicity, resulting in a growing number of tumor survivors with cardiovascular disease. Therefore, a new interdisciplinary subspecialty called "cardio-oncology" has emerged, aiming to detect and treat cardiovascular diseases associated with tumors and antitumor therapies. Recent studies have highlighted the role of ferroptosis in both cardiovascular and neoplastic diseases. The balance between intracellular oxidative stress and antioxidant defense is crucial in regulating ferroptosis. Tumor cells can evade ferroptosis by upregulating multiple antioxidant defense pathways, while many antitumor therapies rely on downregulating antioxidant defense and promoting ferroptosis in cancer cells. Unfortunately, these ferroptosis-inducing antitumor therapies often lack tissue specificity and can also cause injury to the heart, resulting in ferroptosis-induced cardiotoxicity. A range of cardioprotective agents exert cardioprotective effects by inhibiting ferroptosis. However, these cardioprotective agents might diminish the efficacy of antitumor treatment due to their antiferroptotic effects. Most current research on ferroptosis only focuses on either tumor treatment or heart protection but rarely considers both in concert. Therefore, further research is needed to study how to protect the heart during antitumor therapies by regulating ferroptosis. In this review, we summarized the role of ferroptosis in the treatment of neoplastic diseases and cardiovascular diseases and also attempted to propose further research directions for ferroptosis in the field of cardio-oncology.