An integrative pharmacology-based study on the efficacy and mechanism of essential oil of Chaihu Guizhi Decoction on influenza A virus induced pneumonia in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu Guizhi Decoction (CGD) has a long history of use in China for the treatment of influenza, which involves the use of a variety of aromatic herbs. Our previous studies have found that the contents of aromatic constituents in CGD affected the efficacy of treatment of influenza-infected mice, suggesting a clue that essential oil from CGD may play a relatively important role in ameliorating influenza induced pneumonia. AIM OF THE STUDY: To evaluate the anti-influenza potential of essential oil derived from Chaihu Guizhi Decoction (CGD-EO), to characterize and predict the key active components in CGD-EO, and to explore the mechanism of action of CGD-EO. MATERIALS AND METHODS: CGD-EO was obtained by steam distillation, and the components of the essential oil were characterized by gas chromatography-mass spectrometry (GC-MS) in conjunction with the retention index. The constituents absorbed into the blood of mice treated with CGD-EO were analyzed by headspace solid phase microextraction gas chromatography/mass spectrometry (HS-SPME-GC/MS). The potential anti-influenza active constituents and their possible action pathway were predicted by simulation using a network pharmacology approach. The protective effect of CGD-EO and its major components on H1N1/PR8-infected cells was determined using the CCK8 assay kit. Mice infected with influenza A virus H1N1/PR8 were administered different doses of CGD-EO orally and the body weights and lung weights were recorded. Mice with varying degrees of H1N1/PR8 infection were administered CGD-EO orally, and their daily weight, water consumption, and clinical indicators were recorded. Necropsies were conducted on days 3 and 5, during which lung weights were measured and lung tissues were preserved. Furthermore, the mRNA expression of the H1N1/PR8 virus and inflammatory factors in lung tissue was analyzed using RT-qPCR. RESULTS: (E)-cinnamaldehyde was the most abundant compound in the CGD-EO. The results of serum medicinal chemistry combined with network pharmacological analysis indicated that (E)-cinnamaldehyde and 3-phenyl-2-propenal may be potential active components of the CGD-EO anti-influenza, and may be involved in the NF-κB signalling pathway. In vitro studies have demonstrated that both CGD-EO and cinnamaldehyde exert a protective effect on MDCK cells infected with H1N1/PR8. In a 0.5 TCID50 H1N1/PR8-induced influenza model, mice treated with CGD-EO at a dose of 63.50 µg/kg exhibited a reduction in lung index, pathological lung lesions, and H1N1/PR8 viral gene levels. In addition, CGD-EO treatment was found to regulate the levels of inflammatory cytokines, including IL-6, TNF-α, and IFN-γ. Moreover, following three days of administration, an upregulation of NF-κB mRNA levels in mouse lung tissue was observed in response to CGD-EO treatment. CONCLUSIONS: The findings of our study indicate CGD-EO exerts a protective effect against H1N1-induced cytopathic lesions in vitro and is capable of alleviating H1N1-induced pneumonitis in mice. Moreover, it appears to be more efficacious in the treatment of mild symptoms of H1N1 infection. Studies have demonstrated that CGD-EO has antiviral potential to attenuate influenza-induced lung injury by modulating inflammatory cytokines and NF-κB signalling pathways during the early stages of influenza infection. It is possible that (E)-cinnamaldehyde is a potential active ingredient in the anti-influenza efficacy of CGD-EO.

A new strategy for the treatment of intracerebral hemorrhage: Ferroptosis.

Intracerebral hemorrhage, is a cerebrovascular disease with high morbidity, mortality, and disability. Due to the lack of effective clinical treatments, the development of new drugs to treat intracerebral hemorrhage is necessary. In recent years, ferroptosis has been found to play an important role in the pathophysiological process of intracerebral hemorrhage, which can be treated by inhibiting ferroptosis and thus intracerebral hemorrhage. This article aims to explain the mechanism of ferroptosis and its relationship to intracerebral hemorrhage. In the meantime, it briefly discusses the molecules identified to alleviate intracerebral hemorrhage by inhibiting ferroptosis, along with other clinical agents that are expected to treat intracerebral hemorrhage through this mechanism. In addition, a brief overview of the morphological alterations of different forms of cell death and their role in ICH is provided. Finally, the challenges that may arise in translating ferroptosis inhibitors from basic research to clinical use are presented. This article serves as a reference and provides insights to aid in the treatment of intracerebral hemorrhage in the clinic.

OxcarNet: sinc convolutional network with temporal and channel attention for prediction of oxcarbazepine monotherapy responses in patients with newly diagnosed epilepsy.

Objective.Monotherapy with antiepileptic drugs (AEDs) is the preferred strategy for the initial treatment of epilepsy. However, an inadequate response to the initially prescribed AED is a significant indicator of a poor long-term prognosis, emphasizing the importance of precise prediction of treatment outcomes with the initial AED regimen in patients with epilepsy.Approach. We introduce OxcarNet, an end-to-end neural network framework developed to predict treatment outcomes in patients undergoing oxcarbazepine monotherapy. The proposed predictive model adopts a Sinc Module in its initial layers for adaptive identification of discriminative frequency bands. The derived feature maps are then processed through a Spatial Module, which characterizes the scalp distribution patterns of the electroencephalography (EEG) signals. Subsequently, these features are fed into an attention-enhanced Temporal Module to capture temporal dynamics and discrepancies. A channel module with an attention mechanism is employed to reveal inter-channel dependencies within the output of the Temporal Module, ultimately achieving response prediction. OxcarNet was rigorously evaluated using a proprietary dataset of retrospectively collected EEG data from newly diagnosed epilepsy patients at Nanjing Drum Tower Hospital. This dataset included patients who underwent long-term EEG monitoring in a clinical inpatient setting.Main results.OxcarNet demonstrated exceptional accuracy in predicting treatment outcomes for patients undergoing Oxcarbazepine monotherapy. In the ten-fold cross-validation, the model achieved an accuracy of 97.27%, and in the validation involving unseen patient data, it maintained an accuracy of 89.17%, outperforming six conventional machine learning methods and three generic neural decoding networks. These findings underscore the model's effectiveness in accurately predicting the treatment responses in patients with newly diagnosed epilepsy. The analysis of features extracted by the Sinc filters revealed a predominant concentration of predictive frequencies in the high-frequency range of the gamma band.Significance. The findings of our study offer substantial support and new insights into tailoring early AED selection, enhancing the prediction accuracy for the responses of AEDs.

Self-Assembly Hypoxic and ROS Dual Response Nano Prodrug as a New Therapeutic Approach for Glaucoma Treatments.

Glaucoma is an irreversible blinding eye disease characterized by retinal ganglion cell (RGC) death.Previous studies have demonstrated that protecting mitochondria and activating the CaMKII/CREB signaling pathway can effectively protect RGC and axon. However, currently treatments are often unsatisfactory, and the pathogenesis of glaucoma requires further elucidation. In this study, a ROS-responsive dual drug conjugate (OLN monomer) is first designed that simultaneously bonds nicotinamide and oleic acid. The conjugate self-assembled into nanoparticles (uhOLN-NPs) through the aggregation of multiple micelles and possesses ROS scavenging capability. Then, a polymer with a hypoxic response function is designed, which encapsulates uhOLN-NPs to form nanoparticles with hypoxic and ROS responses (HOLN-NPs). Under hypoxia in RGCs, the azo bond of HOLN-NPs breaks and releases uhOLN-NPs. Meanwhile, under high ROS conditions, the thioketone bond broke, leading to the dissociation of nano-prodrug. The released nicotinamide and oleic acid co-scavenge ROS and activate the CaMKII/CREB pathway, protecting mitochondria in RGCs. HOLN-NPs exhibit a significantly superior protective effect on R28 cells in glutamate models of glaucoma. The accumulation of HOLN-NPs in retinal RGCs lead to significant inhibition of RGC apoptosis and axonal damage in vivo. Notably, HOLN-NPs provide a new therapeutic approach for patients with neurodegenerative disease.

Divergent Evolution in Bilateral Prostate Cancer: a Case Study.

Multifocal prostate cancer is a prevalent phenomenon, with most cases remaining uncharacterized from a genomic perspective. A patient presented with bilateral prostate cancer. On systematic biopsy, two indistinguishable clinicopathologic lesions were detected. Whole-genome sequencing displayed somatically unrelated tumours with distinct driver CNA regions, suggesting independent origins of the two tumors. We demonstrated that similar clinicopathologic multifocal tumours, which might be interpreted as clonal disease, can in fact represent independent cancers. Genetic prognostics can prevent mischaracterization of multifocal disease to enable optimal patient management.

Inherent preference for polyunsaturated fatty acids instigates ferroptosis of Treg cells that aggravates high-fat-diet-related colitis.

Inflammatory bowel disease (IBD) has high prevalence in Western counties. The high fat content in Western diets is one of the leading causes for this prevalence; however, the underlying mechanisms have not been fully defined. Here, we find that high-fat diet (HFD) induces ferroptosis of intestinal regulatory T (Treg) cells, which might be the key initiating step for the disruption of immunotolerance and the development of colitis. Compared with effector T cells, Treg cells favor lipid metabolism and prefer polyunsaturated fatty acids (PUFAs) for the synthesis of membrane phospholipids. Therefore, consumption of HFD, which has high content of PUFAs such as arachidonic acid, cultivates vulnerable Tregs that are fragile to lipid peroxidation and ferroptosis. Treg-cell-specific deficiency of GPX4, the key enzyme in maintaining cellular redox homeostasis and preventing ferroptosis, dramatically aggravates the pathogenesis of HFD-induced IBD. Taken together, these studies expand our understanding of IBD etiology.

Phospholipid peroxidation in macrophage confers tumor resistance by suppressing phagocytic capability towards ferroptotic cells.

Ferroptosis holds significant potential for application in cancer therapy. However, ferroptosis inducers are not cell-specific and can cause phospholipid peroxidation in both tumor and non-tumor cells. This limitation greatly restricts the use of ferroptosis therapy as a safe and effective anticancer strategy. Our previous study demonstrated that macrophages can engulf ferroptotic cells through Toll-like receptor 2 (TLR2). Despite this advancement, the precise mechanism by which phospholipid peroxidation in macrophages affects their phagocytotic capability during treatment of tumors with ferroptotic agents is still unknown. Here, we utilized flow sorting combined with redox phospholipidomics to determine that phospholipid peroxidation in tumor microenvironment (TME) macrophages impaired the macrophages ability to eliminate ferroptotic tumor cells by phagocytosis, ultimately fostering tumor resistance to ferroptosis therapy. Mechanistically, the accumulation of phospholipid peroxidation in the macrophage endoplasmic reticulum (ER) repressed TLR2 trafficking to the plasma membrane and caused its retention in the ER by disrupting the interaction between TLR2 and its chaperone CNPY3. Subsequently, this ER-retained TLR2 recruited E3 ligase MARCH6 and initiated the proteasome-dependent degradation. Using redox phospholipidomics, we identified 1-steaoryl-2-15-HpETE-sn-glycero-3-phosphatidylethanolamine (SAPE-OOH) as the crucial mediator of these effects. Conclusively, our discovery elucidates a novel molecular mechanism underlying macrophage phospholipid peroxidation-induced tumor resistance to ferroptosis therapy and highlights the TLR2-MARCH6 axis as a potential therapeutic target for cancer therapy.

Sepsis Biomarkers: Advancements and Clinical Applications-A Narrative Review.

Sepsis is now defined as a life-threatening syndrome of organ dysfunction triggered by a dysregulated host response to infection, posing significant challenges in critical care. The main objective of this review is to evaluate the potential of emerging biomarkers for early diagnosis and accurate prognosis in sepsis management, which are pivotal for enhancing patient outcomes. Despite advances in supportive care, traditional biomarkers like C-reactive protein and procalcitonin have limitations, and recent studies have identified novel biomarkers with increased sensitivity and specificity, including circular RNAs, HOXA distal transcript antisense RNA, microRNA-486-5p, protein C, triiodothyronine, and prokineticin 2. These emerging biomarkers hold promising potential for the early detection and prognostication of sepsis. They play a crucial role not only in diagnosis but also in guiding antibiotic therapy and evaluating treatment effectiveness. The introduction of point-of-care testing technologies has brought about a paradigm shift in biomarker application, enabling swift and real-time patient evaluation. Despite these advancements, challenges persist, notably concerning biomarker variability and the lack of standardized thresholds. This review summarizes the latest advancements in sepsis biomarker research, spotlighting the progress and clinical implications. It emphasizes the significance of multi-biomarker strategies and the feasibility of personalized medicine in sepsis management. Further verification of biomarkers on a large scale and their integration into clinical practice are advocated to maximize their efficacy in future sepsis treatment.

TLR3/TRIF and MAVS Signaling Is Essential in Regulating Mucosal T Cell Responses during Rotavirus Infection.

The functions of the natural dsRNA sensors TLR3 (TRIF) and RIG-I (MAVS) are crucial during viral challenge and have not been accurately clarified in adaptive immune responses to rotavirus (RV) infection. In this study, we found that RV infection caused severe pathological damage to the small intestine of TLR3-/- and TRIF-/- mice. Our data found that dendritic cells from TLR3-/- and TRIF-/- mice had impaired Ag presentation to the RV and attenuated initiation of T cells upon viral infection. These attenuated functions resulted in impaired CD4+ T and CD8+ T function in mice lacking TLR3-TRIF signaling postinfection. Additionally, attenuated proliferative capacity of T cells from TLR3-/- and TRIF-/- mice was observed. Subsequently, we observed a significant reduction in the absolute number of memory T cells in the spleen and mesenteric lymph node (MLN) of TRIF-/- recipient mice following RV infection in a bone marrow chimeric model. Furthermore, there was reduced migration of type 2 classical dendritic cells from the intestine to MLNs after RV infection in TLR3-/- and TRIF-/- mice. Notably, RV infection resulted in attenuated killing of spleen and MLN tissues in TRIF-/- and MAVS-/- mice. Finally, we demonstrated that RV infection promoted apoptosis of CD8+ T cells in TRIF-/- and TLR3-/-MAVS-/- mice. Taken together, our findings highlight an important mechanism of TLR3 signaling through TRIF in mucosal T cell responses to RV and lay the foundation for the development of a novel vaccine.

FAM134B deletion exacerbates apoptosis and epithelial-to-mesenchymal transition in rat lungs exposed to hyperoxia.

Oxygen therapy is widely used in clinical practice; however, prolonged hyperoxia exposure may result in hyperoxic acute lung injury (HALI). In this study, we investigated the role of FAM134B in hyperoxia-induced apoptosis, cell proliferation, and epithelial-to-mesenchymal transition (EMT) using RLE-6TN cells and rat lungs. We also studied the effect of CeO2-NPs on RLE-6TN cells and lungs following hyperoxia exposure. FAM134B was inhibited in RLE-6TN cells and rat lungs following hyperoxia exposure. Overexpressing FAM134B promoted cell proliferation, and reduced EMT and apoptosis following hyperoxia exposure. FAM134B activation increased ER-phagy, decreased apoptosis, improved lung structure damage, and decreased collagen fiber deposition to limit lung injury. These effects could be reversed by PI3K/AKT pathway inhibitor LY294002. Additionally, CeO2-NPs protected RLE-6TN cells and lung damage following hyperoxia exposure by ameliorating impaired ER-phagy. Therefore, FAM134B restoration is a potential therapeutic target for the HALI. Moreover, CeO2-NPs can be used for the treatment of HALI.

Targeting Notch signaling pathways with natural bioactive compounds: a promising approach against cancer.

Notch signaling pathway is activated abnormally in solid and hematological tumors, which perform essential functions in cell differentiation, survival, proliferation, and angiogenesis. The activation of Notch signaling and communication among Notch and other oncogenic pathways heighten malignancy aggressiveness. Thus, targeting Notch signaling offers opportunities for improved survival and reduced disease incidence. Already, most attention has been given to its role in the cancer cells. Recent research shows that natural bioactive compounds can change signaling molecules that are linked to or interact with the Notch pathways. This suggests that there may be a link between Notch activation and the growth of tumors. Here, we sum up the natural bioactive compounds that possess inhibitory effects on human cancers by impeding the Notch pathway and preventing Notch crosstalk with other oncogenic pathways, which provoke further study of these natural products to derive rational therapeutic regimens for the treatment of cancer and develop novel anticancer drugs. This review revealed Notch as a highly challenging but promising target in oncology.

Dietary inflammatory index and its impact on severity and recurrence of Tourette syndrome in children.

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the presence of motor and vocal tics, typically beginning in childhood. Despite significant research efforts, the exact pathophysiology of TS remains incompletely understood. Recent studies suggest that inflammation may play a role in the severity and progression of TS, pointing to the potential influence of dietary and lifestyle factors on the condition. Currently, research on the specific connection between dietary inflammatory index (DII) and TS is still in its early stages, requiring additional clinical and epidemiological studies to validate the strength and specific mechanisms of this connection. AIM: To investigate the association between DII and the severity, recurrence, and inflammatory levels of TS in children. METHODS: A total of 207 children diagnosed with TS in the pediatric department of Qingdao Chengyang People's Hospital from January 2022 to January 2023 were selected. They were divided into stable and unstable groups based on follow-up conditions. Before enrollment, general information of the children [age, gender, body mass index (BMI), guardian's education level, DII score, medical history, family history, academic stress, electronic device usage, medication, and disease progression] was assessed, and serum inflammatory levels were measured during follow-up visits. DII scores and Yale Global Tic Severity Scale (YGTSS) scores were calculated. Furthermore, based on YGTSS scores, the children were classified into mild, moderate, and severe groups. The DII, interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α) levels in each group were compared. RESULTS: Follow-up surveys were completed by 207 children and their guardians. Among them, 117 children were in the stable group, and 90 were in the recurrent group. We found no statistically significant differences in age, gender, comorbidities, BMI, and disease duration between the two groups (P > 0.05). However, academic stress, electronic device usage, medication, guardian's education level, and DII scores showed statistically significant differences between the groups (P < 0.05). Multifactorial regression analysis revealed that guardian's anxiety level, DII score, medication, academic stress, and family history were statistically significant factors (P < 0.05) affecting the recurrence of TS in children. Therefore, anxiety level, DII score, medication status, electronic device usage, and academic stress were identified as factors influencing the recurrence of TS in children. Among them, DII score, academic stress, and family history had odds ratios (OR) greater than 1, indicating risk factors, whereas medication status and guardian's education level had OR values less than 1, indicating protective factors. According to the YGTSS scores, children were categorized into mild, moderate, and severe groups. Comparative analysis of DII and inflammatory levels in children with different degrees of tic disorders revealed that the severe group had the highest DII and inflammatory levels, followed by the moderate group, and the mild group had the lowest levels. The trend of TS progression was consistent with the DII results. Receiver operating characteristic curves were plotted to predict disease progression in patients with TS via inflammatory markers. The areas under the curve for IL-6, CRP, and TNF-α were 0.894 (95%CI: 0.817-0.969), 0.793 (95%CI: 0.694-0.893), and 0.728 (95%CI: 0.614-0.843) respectively, with statistically significant differences (P < 0.05). According to the Youden index, the optimal cutoff values were IL-6 = 3.775 ng/L (sensitivity 68.1% and specificity 68.4%), CRP = 6.650 mg/L (sensitivity 60.6% and specificity 68.4%), and TNF-α = 0.666 (sensitivity 60.6% and specificity 71.1%). CONCLUSION: We found a certain correlation between DII and the severity, recurrence, and inflammatory levels of TS in children. Reasonable reduction in the intake of pro-inflammatory foods may be beneficial in reducing the risk of disease progression in children with TS.

Intelligent medicine in focus: the 5 stages of evolution in robot-assisted surgery for prostate cancer in the past 20 years and future implications.

Robot-assisted surgery has evolved into a crucial treatment for prostate cancer (PCa). However, from its appearance to today, brain-computer interface, virtual reality, and metaverse have revolutionized the field of robot-assisted surgery for PCa, presenting both opportunities and challenges. Especially in the context of contemporary big data and precision medicine, facing the heterogeneity of PCa and the complexity of clinical problems, it still needs to be continuously upgraded and improved. Keeping this in mind, this article summarized the 5 stages of the historical development of robot-assisted surgery for PCa, encompassing the stages of emergence, promotion, development, maturity, and intelligence. Initially, safety concerns were paramount, but subsequent research and engineering advancements have focused on enhancing device efficacy, surgical technology, and achieving precise multi modal treatment. The dominance of da Vinci robot-assisted surgical system has seen this evolution intimately tied to its successive versions. In the future, robot-assisted surgery for PCa will move towards intelligence, promising improved patient outcomes and personalized therapy, alongside formidable challenges. To guide future development, we propose 10 significant prospects spanning clinical, research, engineering, materials, social, and economic domains, envisioning a future era of artificial intelligence in the surgical treatment of PCa.

Hepatic microcirculatory disturbance in liver diseases: intervention with traditional Chinese medicine.

The liver, a complex parenchymal organ, possesses a distinctive microcirculatory system crucial for its physiological functions. An intricate interplay exists between hepatic microcirculatory disturbance and the manifestation of pathological features in diverse liver diseases. This review updates the main characteristics of hepatic microcirculatory disturbance, including hepatic sinusoidal capillarization, narrowing of sinusoidal space, portal hypertension, and pathological angiogenesis, as well as their formation mechanisms. It also summarized the detection methods for hepatic microcirculation. Simultaneously, we have also reviewed the characteristics of microcirculatory disturbance in diverse liver diseases such as acute liver failure, hepatic ischemia-reperfusion injury, viral hepatitis, non-alcoholic fatty liver disease, hepatic fibrosis, hepatic cirrhosis, and hepatocellular carcinoma. Finally, this review also summarizes the advancement in hepatic microcirculation attributed to traditional Chinese medicine (TCM) and its active metabolites, providing novel insights into the application of TCM in treating liver diseases.

Heterosis formation mechanism, prediction methods, and their application and prospect in pig production.

Heterosis is the phenomenon that the hybrid offspring outperform two-parent population. Hybridisation has been widely used in plant and animal production as it effectively improves the growth and developmental performance, reproductive performance and disease resistance of the offspring. Hybridization can effectively improve the growth and development performance, reproductive performance and disease resistance of offspring, so it is widely used in animal and plant production. Researchers have used cross-breeding techniques to cultivate excellent new agricultural and animal husbandry strains and supporting lines such as super-excellent Chaoyou 1000 hybrid rice, Xiaoyan No.6 hybrid wheat, Dumeng sheep, and Shanxia black pigs. However, there are still some urgent problems in the current hybrid dominance research: the existing hybrid dominance theory can only partially explain the phenomenon of plant and animal hybrid dominance, and the theory of animal hybrid dominance is less researched, and the accuracy of the existing hybrid dominance prediction methods is limited. China is the world's largest pork production and consumption country. Heterosis can effectively improve the production performance of pigs, and its application in the pig industry has important economic and research value. However, the existing research on pig hybrid production is in its infancy and needs to be further studied. In this review, we summarize the existing heterosis theory, heterosis prediction methods, and their application in pig production, to provide a reference for the application of heterosis in pig breeding.

How the perfectionistic climate of a sports team predicts the athletic performance of elite athletes: a case study of the CUBAL women's basketball team.

Objective: In competitive sports, understanding how the perfectionistic climate within teams influences the performance of elite female athletes can provide valuable insights for enhancing coaching practice and athletic achievement. Based on the cognitive appraisal theory of stress, this study constructs a dual-path model using stressors and coping strategies as mediators, referred to as the Perfectionistic Climate on Athletic Performance model (PCPM). The study explores the predictive role of the perfectionistic climate within sports teams on the athletic performance of elite female basketball players. Methods: The empirical study the relationships among the variables in the model using a sample of 125 core players from the top-level women's basketball teams in the 24th CUBAL24 tournament in 2022. A Structural Equation Modeling (SEM) analysis was conducted using AMOS 20.0, primarily employing the bias-corrected Bootstrap method to test the dual-path model. Results: The findings reveal double-edged paths towards a perfectionistic climate on athletic performance. In the positive pathway, a perfectionistic climate can positively predict athletic performance through challenge-related sources of stress and positive coping strategies. In the negative pathway, a perfectionistic climate can negatively predict athletic performance through threat-related sources of stress and negative coping strategies. Conclusion: Coaches need to pay attention to athletes' cognitive evaluations of the perfectionistic climate as a source of pressure. By setting challenging goals, coaches can guide athletes to view the perfectionistic climate of the sports team as a source of challenging pressure, thus unleashing their potential. Coaches should actively guide athletes in coping with the pressure brought about by the perfectionistic climate, enhancing their ability to handle stress. This will enable athletes to better adapt to the team's perfectionistic climate and further improve individual and team athletic performance.

[Treatment of hypoxia-induced ED in high-altitude areas by transcutaneous low-frequency electrical stimulation based on the parameters obtained from visualized precision electrophysiological diagnosis].

OBJECTIVE: To investigate the effects of visualized precision electrophysiological diagnosis and transcutaneous low-frequency electrical stimulation (TES) on hypoxia-induced ED in high-altitude areas. METHODS: This study included 152 ED patients from high-altitude hypoxic areas treated by TES based on the parameters obtained from visualized precision electrophysiological diagnosis. We followed up the patients for 1 to 3 months and compared their IIEF-5 scores, nocturnal penile tumescence and rigidity (NPTR) and infrared thermal metabolic technology (TMT)-based temperature of the whole body and diseased parts before and after treatment. RESULTS: All the patients successfully completed 1 to 3 courses of TES. There were no statistically significant differences in the IIEF-5 scores (P<0.05) and penile tip optimal erection rigidity and duration (P<0.01) of the patients before and after treatment. TMT images indicated a temperature change of >1.5 ℃ in the penis and bilateral inguinal regions after treatment, suggesting the effectiveness of electrical stimulation. No recurrence was observed during the follow-up. CONCLUSION: TES based on the parameters obtained from visualized precision electrophysiological diagnosis has a definite effect on hypoxia-induced ED by enhancing oxygen supply to the penile corpus cavernosum and improving its function and structure.

A genome-wide methylation analysis of Chinese Han patients with chronic insomnia disorder.

BACKGROUND: As the most common sleep disorder, chronic insomnia disorder (CID) has become a global health burden to the public. However, it remains unclear about the pathogenesis of this disease. Epigenetic changes may provide important insights into the gene-environment interaction in CID. Therefore, this study was conducted to investigate the DNA methylation pattern in CID and reveal the epigenetic mechanism of this disease. METHODS: In this study, whole blood DNA was extracted from 8 CID patients (the CID group) and 8 healthy controls (the control group), respectively. Besides, genome-wide DNA methylation was detected by Illumina Human Methylation 850 K Beadchip. Moreover, the sleep quality and insomnia severity were evaluated by the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI), respectively. RESULTS: A total of 369 differentially methylated positions (DMPs) and 23 differentially methylated regions (DMRs) were identified between the CID and control groups. LHX6 was identified as the most important differentially methylated gene (DMG). The Gene Ontology (GO) analysis results corroborated that DMPs were significantly enriched in 105 GO terms, including cell signaling, homogenous cell adhesion of plasma membrane adhesion molecules, nervous system development, cell adhesion, and calcium ion binding. In addition, it was demonstrated that DMPs were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including the hippo signaling pathway, Ras signaling pathway, and vitamin B6 metabolism. The DMR-related GO analysis results revealed the positive regulation of protein kinase activities. CONCLUSIONS: DNA methylation plays a critical role in the development of CID, and LHX6 is validated to be an important DMG.

Development and evaluation of a second victim training course for nursing managers.

BACKGROUND: Most nursing managers are not fully aware of second victims and may not be able to provide support. Moreover, there are relatively few training courses for nursing managers about second victims. AIM: To describe the construction and evaluation of a second victim course for nursing managers. DESIGN: A single-group pretest-posttest study design was used. SETTING: A large comprehensive tertiary hospital with over 3000 beds in China. PARTICIPANTS: Forty-nine nursing managers who met the inclusion and exclusion criteria participated in this training. Sixteen clinical frontline nurses who experienced adverse events within three months following the training were also invited. METHODS: The course "Second Victim & Empathy Communication" was developed through a literature review and expert consultation and consisted of 4 unit modules: (1) adverse events & second victims, (2) the recovery trajectory of second victims, (3) second victim supportive resources, and (4) key strategies of empathy communication. A course evaluation questionnaire, an empathy communication questionnaire for nursing managers, a second victim evaluation questionnaire, and an open-ended question were used to measure the feasibility, acceptability and effectiveness of the course. RESULTS: >97.96 % of the nursing managers were satisfied with the course, >97.96 % had learned new knowledge, and >95.92 % had changed their behavior and attitudes toward second victims. Their levels of empathetic communication differed significantly before and after training (t = -2.170, P = 0.035). Among these nursing managers, twenty-six participants provided positive and meaningful feedback and suggestions to the course by answering an open-ended question. A total of 66.6 % to 100 % of second victims were satisfied with the empathetic communication behavior exhibited by nursing managers. CONCLUSION: The second victim training course is feasible and can be used for clinical training to enhance nursing managers' understanding of second victims and enhance their empathetic communication.

BCL6 confers resistance to HDAC inhibitors in DLBCL.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with limited response to chemotherapy. Histone acetylation is reduced in DLBCL. Chidamide, a histone deacetylase inhibitor, shows promise in lymphomas but needs further investigation for DLBCL. Our study indicated that chidamide effectively suppresses DLBCL both in vitro and in vivo. High-throughput RNA sequencing analysis provided comprehensive evidence that chidamide markedly influences crucial signaling pathways in DLBCL, including the MAPK, MYC and p53 pathway. Additionally, we observed substantial variability in the sensitivity of DLBCL cells to chidamide, and identified that elevated expression of BCL6 might confer resistance to chidamide in DLBCL. Moreover, our investigations revealed that BCL6 inhibited chidamide-induced histone acetylation by recruiting histone deacetylase (HDACs), leading to drug resistance in DLBCL cells. Furthermore, we found that lenalidomide targeted BCL6 degradation through the ubiquitination pathway and restore the sensitivity of drug-resistant DLBCL to chidamide. Collectively, these findings provided valuable insights into the global impact of chidamide on DLBCL and highlight the potential of targeting HDACs as a therapeutic strategy for DLBCL. Identifying BCL6 as a biomarker for predicting the response to chidamide and the combination therapy with BCL6 inhibition has the potential to lead to more personalized and effective treatments for DLBCL patients.