Clinical characteristics and anticoagulation patterns of patients with acute pulmonary thromboembolism and hemoptysis.

Hemoptysis is a frequently encountered manifestation in cases of acute pulmonary thromboembolism (PTE), significantly impacting clinical decision-making. Despite its clinical relevance, studies focusing on patients with acute PTE and hemoptysis are notably scarce. In this retrospective study, we examined data from hospitalized patients with acute PTE at Peking Union Medical College Hospital (PUMCH) between January 2012 and October 2020. Among the 896 patients analyzed, 105 (11.7%) presented with hemoptysis. Patients with hemoptysis were younger, had higher RRs, and frequently reported chest pain, predominantly showing a negative sPESI score. A significant association with autoimmune diseases was observed (39.0% vs. 16.1%; p < 0.001), along with higher occurrences of pulmonary infections (29.5%), lung cancer (21.0%), and chronic heart failure (16.2%). Hemoptysis in PTE is multifactorial; 51.4% of cases were PTE-related, with 85.2% experiencing mild hemoptysis. Among patients with disease-related hemoptysis (13.3%), 90.9% with massive hemoptysis had underlying diseases, predominantly lung cancer. In 35.2% of cases, the cause of hemoptysis remained undetermined, with vasculitis accounting for 29.7%. Anticoagulation strategies varied with the severity of hemoptysis; 82.9% with mild and only 27.3% with massive hemoptysis received therapeutic-dose anticoagulation. Multivariate analysis identified massive hemoptysis as the most significant determinant of anticoagulation decisions. Patients with massive hemoptysis had the poorest outcomes, with an in-hospital mortality rate of 36.4% and 72.7% receiving reduced or no anticoagulation.

Heparin is an effective treatment for preventing liver failure after hepatectomy.

BACKGROUND: Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver function through a number of mechanisms, and thus, prevent liver failure. AIM: To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy. METHODS: The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) v1. 4 pinpointed patients who had undergone hepatectomy for liver cancer, subdividing them into two cohorts: Those who were injected with heparin and those who were not. The statistical evaluations used were unpaired t-tests, Mann-Whitney U tests, chi-square tests, and Fisher's exact tests to assess the effect of heparin administration on PHLF, duration of intensive care unit (ICU) stay, need for mechanical ventilation, use of continuous renal replacement therapy (CRRT), incidence of hypoxemia, development of acute kidney injury, and ICU mortality. Logistic regression was utilized to analyze the factors related to PHLF, with propensity score matching (PSM) aiming to balance the preoperative disparities between the two groups. RESULTS: In this study, 1388 patients who underwent liver cancer hepatectomy were analyzed. PSM yielded 213 matched pairs from the heparin-treated and control groups. Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples. Further analysis in the matched cohorts confirmed a significant association, with heparin reducing the risk of PHLF (odds ratio: 0.518; 95% confidence interval: 0.295-0.910; P = 0.022). Additionally, heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations, diminished requirements for respiratory support and CRRT, and lower incidences of hypoxemia and ICU mortality. CONCLUSION: Liver failure is an important hazard following hepatic surgery. During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure. This indicates that heparin may provide a hopeful option for controlling PHLF.

Biochemical indicators, cell apoptosis, and metabolomic analyses of the low-temperature stress response and cold tolerance mechanisms in Litopenaeus vannamei.

The cold tolerance of Litopenaeus vannamei is important for breeding in specific areas. To explore the cold tolerance mechanism of L. vannamei, this study analyzed biochemical indicators, cell apoptosis, and metabolomic responses in cold-tolerant (Lv-T) and common (Lv-C) L. vannamei under low-temperature stress (18 °C and 10 °C). TUNEL analysis showed a significant increase in apoptosis of hepatopancreatic duct cells in L. vannamei under low-temperature stress. Biochemical analysis showed that Lv-T had significantly increased levels of superoxide dismutase (SOD) and triglycerides (TG), while alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH-L), and uric acid (UA) levels were significantly decreased compared to Lv-C (p < 0.05). Metabolomic analysis displayed significant increases in metabolites such as LysoPC (P-16:0), 11beta-Hydroxy-3,20-dioxopregn-4-en-21-oic acid, and Pirbuterol, while metabolites such as 4-Hydroxystachydrine, Oxolan-3-one, and 3-Methyldioxyindole were significantly decreased in Lv-T compared to Lv-C. The differentially regulated metabolites were mainly enriched in pathways such as Protein digestion and absorption, Central carbon metabolism in cancer and ABC transporters. Our study indicate that low temperature induces damage to the hepatopancreatic duct of shrimp, thereby affecting its metabolic function. The cold resistance mechanism of Lv-T L. vannamei may be due to the enhancement of antioxidant enzymes and lipid metabolism.

Roles of Two-Dimensional Materials in Antibiofilm Applications: Recent Developments and Prospects.

Biofilm-associated infections pose a significant challenge in healthcare, constituting 80% of bacterial infections and often leading to persistent, chronic conditions. Conventional antibiotics struggle with efficacy against these infections due to the high tolerance and resistance induced by bacterial biofilm barriers. Two-dimensional nanomaterials, such as those from the graphene family, boron nitride, molybdenum disulfide (MoS2), MXene, and black phosphorus, hold immense potential for combating biofilms. These nanomaterial-based antimicrobial strategies are novel tools that show promise in overcoming resistant bacteria and stubborn biofilms, with the ability to circumvent existing drug resistance mechanisms. This review comprehensively summarizes recent developments in two-dimensional nanomaterials, as both therapeutics and nanocarriers for precision antibiotic delivery, with a specific focus on nanoplatforms coupled with photothermal/photodynamic therapy in the elimination of bacteria and penetrating and/or ablating biofilm. This review offers important insight into recent advances and current limitations of current antibacterial nanotherapeutic approaches, together with a discussion on future developments in the field, for the overall benefit of public health.

The impact of tertiary lymphoid structures on tumor prognosis and the immune microenvironment in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a common malignancy whose prognosis and treatment outcome are influenced by many factors. Some studies have found that tertiary lymphoid structures (TLSs) in cancer may contribute to prognosis and the prediction of immunotherapy efficacy However, the combined role of TLSs in NSCLC remains unclear. We accessed The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to obtain mRNA sequencing data and clinical information as the TCGA cohort, and used our own sample of 53 advanced NSCLC as a study cohort. The samples were divided into TLS+ and TLS- groups by pathological tissue sections. Patients of the TLS+ group had a better OS (p = 0.022), PFS (p = 0.042), and DSS (p = 0.004) in the TCGA cohort, and the results were confirmed by the study cohort (PFS, p = 0.012). Furthermore, our result showed that the count and size of TLSs are closely associated with the efficacy of immunotherapy. In addition, the TLS+ group was associated with better immune status and lower tumor mutation load. In the tumor microenvironment (TME), the expression levels of CD4+ T cells and CD8+ T cells of different phenotypes were associated with TLSs. Overall, TLSs are a strong predictor of survival and immunotherapeutic efficacy in advanced NSCLC, and T cell-rich TLSs suggest a more ordered and active immune response site, which aids in the decision-making and application of immunotherapy in the clinic.

Predicting hepatocellular carcinoma: A new non-invasive model based on shear wave elastography.

BACKGROUND: Integrating conventional ultrasound features with 2D shear wave elastography (2D-SWE) can potentially enhance preoperative hepatocellular carcinoma (HCC) predictions. AIM: To develop a 2D-SWE-based predictive model for preoperative identification of HCC. METHODS: A retrospective analysis of 884 patients who underwent liver resection and pathology evaluation from February 2021 to August 2023 was conducted at the Oriental Hepatobiliary Surgery Hospital. The patients were divided into the modeling group (n = 720) and the control group (n = 164). The study included conventional ultrasound, 2D-SWE, and preoperative laboratory tests. Multiple logistic regression was used to identify independent predictive factors for malignant liver lesions, which were then depicted as nomograms. RESULTS: In the modeling group analysis, maximal elasticity (Emax) of tumors and their peripheries, platelet count, cirrhosis, and blood flow were independent risk indicators for malignancies. These factors yielded an area under the curve of 0.77 (95% confidence interval: 0.73-0.81) with 84% sensitivity and 61% specificity. The model demonstrated good calibration in both the construction and validation cohorts, as shown by the calibration graph and Hosmer-Lemeshow test (P = 0.683 and P = 0.658, respectively). Additionally, the mean elasticity (Emean) of the tumor periphery was identified as a risk factor for microvascular invasion (MVI) in malignant liver tumors (P = 0.003). Patients receiving antiviral treatment differed significantly in platelet count (P = 0.002), Emax of tumors (P = 0.033), Emean of tumors (P = 0.042), Emax at tumor periphery (P < 0.001), and Emean at tumor periphery (P = 0.003). CONCLUSION: 2D-SWE's hardness value serves as a valuable marker for enhancing the preoperative diagnosis of malignant liver lesions, correlating significantly with MVI and antiviral treatment efficacy.

Meta-transcriptomic analysis of companion animal infectomes reveals their diversity and potential roles in animal and human disease.

Companion animals such as cats and dogs harbor diverse microbial communities that can potentially impact human health due to close and frequent contact. To better characterize their total infectomes and assess zoonotic risks, we characterized the overall infectomes of companion animals (cats and dogs) and evaluated their potential zoonotic risks. Meta-transcriptomic analyses were performed on 239 samples from cats and dogs collected across China, identifying 24 viral species, 270 bacterial genera, and two fungal genera. Differences in the overall microbiome and infectome composition were compared across different animal species (cats or dogs), sampling sites (rectal or oropharyngeal), and health status (healthy or diseased). Diversity analyses revealed that viral abundance was generally higher in diseased animals compared to healthy ones, while differences in microbial composition were mainly driven by sampling site, followed by animal species and health status. Disease association analyses validated the pathogenicity of known pathogens and suggested potential pathogenic roles of previously undescribed bacteria and newly discovered viruses. Cross-species transmission analyses identified seven pathogens shared between cats and dogs, such as alphacoronavirus 1, which was detected in both oropharyngeal and rectal swabs albeit with differential pathogenicity. Further analyses showed that some viruses, like alphacoronavirus 1, harbored multiple lineages exhibiting distinct pathogenicity, tissue, or host preferences. Ultimately, a systematic evolutionary screening identified 27 potential zoonotic pathogens in this sample set, with far more bacterial than viral species, implying potential health threats to humans. Overall, our meta-transcriptomic analysis reveals a landscape of actively transcribing microorganisms in major companion animals, highlighting key pathogens, those with the potential for cross-species transmission, and possible zoonotic threats. IMPORTANCE: This study provides a comprehensive characterization of the entire community of infectious microbes (viruses, bacteria, and fungi) in companion animals like cats and dogs, termed the "infectome." By analyzing hundreds of samples from across China, the researchers identified numerous known and novel pathogens, including 27 potential zoonotic agents that could pose health risks to both animals and humans. Notably, some of these zoonotic pathogens were detected even in apparently healthy pets, highlighting the importance of surveillance. The study also revealed key microbial factors associated with respiratory and gastrointestinal diseases in pets, as well as potential cross-species transmission events between cats and dogs. Overall, this work sheds light on the complex microbial landscapes of companion animals and their potential impacts on animal and human health, underscoring the need for monitoring and management of these infectious agents.

SHR-A1811 (antibody-drug conjugate) in advanced HER2-mutant non-small cell lung cancer: a multicenter, open-label, phase 1/2 study.

A dose-escalation and expansion, phase 1/2 study (ClinicalTrials.gov, NCT04818333) was conducted to assess the novel antibody-drug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer (NSCLC). Here, we report results from the phase 1 portion. Patients who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 weeks. Dose escalation followed a Bayesian logistic regression model that included overdose control, with subsequent selection of tolerable levels for dose expansion. Overall, 63 patients were enrolled, including 43 receiving a recommended dose for expansion of 4.8 mg/kg. All patients had HER2-mutant disease. Dose-limiting toxicity occurred in one patient in the 8.0 mg/kg dose cohort. Grade ≥ 3 treatment-related adverse events occurred in 29 (46.0%) patients. One patient in the 6.4 mg/kg cohort died due to interstitial lung disease. As of April 11, 2023, the 4.8 mg/kg cohort showed an objective response rate of 41.9% (95% CI 27.0-57.9), and a disease control rate of 95.3% (95% CI 84.2-99.4). The median duration of response was 13.7 months, with 13 of 18 responses ongoing. The median progression-free survival was 8.4 months (95% CI 7.1-15.0). SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutant NSCLC.

Rupture risk of intracranial aneurysms: Comparison between small ruptured intracranial aneurysms and large unruptured intracranial aneurysms.

To compare the differences in clinical and morphological features between small ruptured intracranial aneurysms and large unruptured intracranial aneurysms to evaluate the risk factors for the rupture of IAs. The clinical data of 189 consecutive patients with 193 IAs were reviewed. The patients and IAs were divided into ruptured (<5 mm) and unruptured groups (>10 mm). The characteristics of the patients and the intracranial aneurysms (IAs) were compared between the 2 groups, and the risk factors for rupture of IAs were assessed using multiple logistic regression. Patient age (odds ratio [OR], 0.955), IA located at the internal carotid artery (ICA, OR, 0.202), irregular shape (OR, 0.083) and parent vessel diameter (OR, 0.426) were negatively correlated with the risk of IA rupture. IAs located at bifurcations (OR, 6.766) were positively correlated with the risk of IA rupture. In addition to the size of the IAs, regardless of IAs shape, other factors, such as younger age (<63.5 years), location at a bifurcation, IAs located at the ICA and a small parent vessel diameter (<3.25 mm), can influence the risk of IA rupture.

N-Glycosylation of MRS2 balances aerobic and anaerobic energy production by reducing rapid mitochondrial Mg2+ influx in conditions of high glucose or impaired respiratory chain function.

N-linked glycoproteins function in numerous biological processes, modulating enzyme activities as well as protein folding, stability, oligomerization, and trafficking. While N-glycosylation of mitochondrial proteins has been detected by untargeted MS-analyses, the physiological existence and roles of mitochondrial protein N-linked glycosylation remain under debate. Here, we report that MRS2, a mitochondrial inner membrane protein that functions as the high flux magnesium transporter, is N-glycosylated to various extents depending on cellular bioenergetic status. Both N-glycosylated and unglycosylated isoforms were consistently detected in mitochondria isolated from mouse liver, rat and mouse liver fibroblast cells (BRL 3A and AFT024, respectively) as well as human skin fibroblast cells. Immunoblotting of MRS2 showed it was bound to, and required stringent elution conditions to remove from, lectin affinity columns with covalently bound concanavalin A or Lens culinaris agglutinin. Following peptide:N-glycosidase F (PNGase F) digestion of the stringently eluted proteins, the higher Mr MRS2 bands gel-shifted to lower Mr and loss of lectin affinity was seen. BRL 3A cells treated with two different N-linked glycosylation inhibitors, tunicamycin or 6-diazo-5-oxo-l-norleucine, resulted in decreased intensity or loss of the higher Mr MRS2 isoform. To investigate the possible functional role of MRS2 N- glycosylation, we measured rapid Mg2+ influx capacity in intact mitochondria isolated from BRL 3A cells in control media or following treatment with tunicamycin or 6-diazo-5-oxo-l-norleucine. Interestingly, rapid Mg2+ influx capacity increased in mitochondria isolated from BRL 3A cells treated with either N-glycosylation inhibitor. Forcing reliance on mitochondrial respiration by treatment with either galactose media or the glycolytic inhibitor 2-deoxyglucose or by minimizing glucose concentration similarly reduced the N-glycosylated isoform of MRS2, with a correlated concomitant increase in rapid Mg2+ influx capacity. Conversely, inhibiting mitochondrial energy production in BRL 3A cells with either rotenone or oligomycin resulted in an increased fraction of N-glycosylated MRS2, with decreased rapid Mg2+ influx capacity. Collectively, these data provide strong evidence that MRS2 N-glycosylation is directly involved in the regulation of mitochondrial matrix Mg2+, dynamically communicating relative cellular nutrient status and bioenergetic capacity by serving as a physiologic brake on the influx of mitochondrial matrix Mg2+ under conditions of glucose excess or mitochondrial bioenergetic impairment.

Clinical Characteristics and Prognosis of Acute Pulmonary Embolism with Hemoptysis in Autoimmune Disease Patients.

Background: Hemoptysis is prevalent in acute pulmonary embolism (PE) and significantly influences clinical decision-making. Despite the increasing reports of PE in patients with autoimmune diseases, limited studies have investigated the association between acute PE with hemoptysis and autoimmune disease. Methods: The retrospective study aimed to investigate patients with autoimmune disease who presented with acute PE and hemoptysis at Peking Union Medical College Hospital (PUMCH) between January 2012 and October 2020. A comparative analysis was conducted between patients with and without hemoptysis, as well as between those with autoimmune diseases and those without. Clinical characteristics, PE severity stratification, the amount of hemoptysis, initial anticoagulation management, and prognosis were analyzed descriptively. Results: The study analyzed 896 patients diagnosed with acute PE, of whom 105 (11.7%) presented with hemoptysis. Hemoptysis in PE patients was frequently associated with autoimmune diseases (39%, 41/105), a younger patient population (42.0 vs. 52.7 years old, P =0.002), and a higher prevalence of low-risk PE (53.7 vs. 28.1, P=0.008) compared with non-autoimmune disease patients. Multivariate logistic analysis showed PE patients with primary or metastatic lung cancer, chest pain, age < 48 years old, chronic heart failure, autoimmune disease, pulmonary infection and male were more likely to develop hemoptysis. Patients were grouped based on maximum daily sputum blood volume and PE risk stratification. Most patients (73.2%) received therapeutic-dose anticoagulation. Poor prognosis is observed in patients with moderate to massive hemoptysis and intermediate-high-risk or high-risk PE. Conclusions: Hemoptysis is a relatively common manifestation in patients with PE, and its presence during the diagnostic workup of acute PE necessitates careful analysis of underlying comorbidities. In cases where hemoptysis occurs in individuals with autoimmune diseases in the context of PE, proactive management strategies targeting the primary disease are crucial. Therapeutic decisions should consider both PE severity stratification and the volume of hemoptysis.

Interstitial lung diseases associated with ANCA positivity: A different disease spectrum from interstitial pneumonia with autoimmune features.

BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA) is a type of autoantibodies associated with vasculitis. ANCA positivity is commonly observed in interstitial lung disease (ILD) patients. 7%-10% of ANCA-positive ILD patients don't present any symptoms of systemic vasculitis and are termed ANCA-positive idiopathic interstitial pneumonia (ANCA-IIP). Some researchers propose that ANCA-IIP should be categorized as interstitial pneumonia with autoimmune features (IPAF), although the official ATS/ERS statements exclude ANCA-IIP from this classification. Whether ANCA-IIP should be categorized into the entity of IPAF is still debatable. METHODS: Patients diagnosed with ANCA-IIP and those with IPAF were analyzed in a retrospective study of ILD. The clinical outcomes were determined through pulmonary function tests (PFTs) after a one-year follow-up, as well as assessing all-cause mortality. RESULTS: 27 patients with ANCA-IIP and 143 patients with IPAF were analyzed from a cohort of 995 patients with ILD. Patients in the ANCA-IIP group had an older age and a high proportion of males compared to those in the IPAF group. PFT results at baseline were similar between the two groups, except for a better FEV1% in the ANCA-IIP group. Glucocorticoid and immunosuppressive therapy improved pulmonary function in patients with IPAF, but it continued to deteriorate after one year of treatment in the ANCA-IIP group. Furthermore, the all-cause mortality rate was significantly higher in the ANCA-IIP group than in the IPAF group (22.2% vs. 6.3%, P = 0.017). CONCLUSION: The responses to glucocorticoid and immunosuppressive therapy differ between the ANCA-IIP and IPAF groups, leading to divergent prognoses. Therefore, it is inappropriate to classify ANCA-IIP as part of IPAF.

FUS Selectively Facilitates circRNAs Packing into Small Extracellular Vesicles within Hypoxia Neuron.

Small extracellular vesicles (sEVs) contain abundant circular RNAs (circRNAs) and are involved in cellular processes, particularly hypoxia. However, the process that packaging of circRNAs into neuronal sEVs under hypoxia is unclear. This study revealed the spatial mechanism of the Fused in Sarcoma protein (FUS) that facilitates the loading of functional circRNAs into sEVs in hypoxia neurons. It is found that FUS translocated from the nucleus to the cytoplasm and is more enriched in hypoxic neuronal sEVs than in normal sEVs. Cytoplasmic FUS formed aggregates with the sEVs marker protein CD63 in cytoplasmic stress granules (SGs) under hypoxic stress. Meanwhile, cytoplasmic FUS recruited of functional cytoplasmic circRNAs to SGs. Upon relief of hypoxic stress and degradation of SGs, cytoplasmic FUS is transported with those circRNAs from SGs to sEVs. Validation of FUS knockout dramatically reduced the recruitment of circRNAs from SGs and led to low circRNA loading in sEVs, which is also confirmed by the accumulation of circRNAs in the cytoplasm. Furthermore, it is showed that the FUS Zf_RanBP domain regulates the transport of circRNAs to sEVs by interacting with hypoxic circRNAs in SGs. Overall, these findings have revealed a FUS-mediated transport mechanism of hypoxia-related cytoplasmic circRNAs loaded into sEVs under hypoxic conditions.

Activation of Wnt/ß-catenin signaling promotes immune evasion via the ß-catenin/IKZF1/CCL5 axis in hepatocellular carcinoma.

Immune checkpoint therapy (ICT) has been shown to produce durable responses in various cancer patients. However, its efficacy is notably limited in hepatocellular carcinoma (HCC), with only a small percentage of patients responding positively to treatment. The mechanism underlying resistance to ICT in HCC remains poorly understood. Here, we showed that combination treatment of ICG-001, an inhibitor of the Wnt/ß-catenin signaling pathway, with anti-PD-1 antibody effectively suppresses tumor growth and promotes the infiltration of immune cells such as DCs and CD8+ T cells in the tumor microenvironment (TME). By inhibiting the activity of ß-catenin and blocking its binding to the transcription factor IKAROS family zinc finger 1 (IKZF1), ICG-001 upregulated the expression of CCL5. Moreover, IKZF1 regulated the activity of the CCL5 promoter and its endogenous expression. Through inhibition of the WNT/ß-catenin signaling pathway, upregulation of the expression of CCL5 was achieved, which subsequently recruited more DCs into the TME via C-C motif chemokine receptor 5 (CCR5). This, in turn, resulted in an increase in the infiltration of CD8+ T cells in the TME, thereby enhancing the antitumor immune response. Analysis of a tissue microarray derived from HCC patient samples revealed a positive correlation between survival rate and prognosis and the expression levels of CCL5/CD8. In conclusion, our findings suggest that combined application of ICG-001 and anti-PD-1 antibody exhibits significantly enhanced antitumor efficacy. Hence, combining a WNT/ß-catenin signaling pathway inhibitor with anti-PD-1 therapy may be a promising treatment strategy for patients with HCC.

Knowledge, attitudes, and practices among patients with anemia towards disease management.

Objective: This study aimed to assess the knowledge, attitudes and practices among anemia patients toward disease management. Methods: This web-based cross-sectional study was conducted between September and December 2023 at The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine). A self-designed questionnaire was developed to collect demographic information of anemia patients, and assess their knowledge, attitudes and practices (KAP) toward disease management. Results: A total of 396 valid questionnaires were collected. The mean age of the participants was 57.44 ± 16.80 years, and 52.02% were female. The mean knowledge, attitudes, and practices scores were 11.47 ± 1.73 (possible range: 0-14), 27.32 ± 2.96 (possible range: 7-35), and 40.49 ± 6.06 (possible range: 10-50), respectively. Multivariate analysis showed that bachelor's degree or above was independently associated with sufficient knowledge (OR = 2.372, 95%CI: 1.160-4.853, p = 0.018). Knowledge (OR = 1.350, 95%CI: 1.166-1.563, p < 0.001) and hemoglobin within 60-90 g/L (OR = 1.782, 95%CI: 1.090-2.912, p = 0.021) were independently associated with positive attitudes. Moreover, attitudes (OR = 1.618, 95%CI: 1.454-1.799, p < 0.001) and diagnosis ≥1 year (OR = 1.949, 95%CI: 1.171-3.243, p = 0.010) were independently associated with proactive practices. The path analysis demonstrated that knowledge was directly and positively correlated with attitudes (ß = 0.484, 95% CI: 0.363-0.647, p = 0.008), and attitudes was directly and positively correlated with practices (ß = 1.195, 95% CI: 1.062-1.332, p = 0.007). Moreover, knowledge was indirectly and positively correlated with practice (ß = 0.579, 95% CI: 0.434-0.805, p = 0.004). Conclusion: Anemia patients have sufficient knowledge, negative attitudes, but proactive practices toward the toward disease management Comprehensive training programs are needed to improve anemia patients practices in this area.

Evaluation of system based psychological first aid training on the mental health proficiency of emergency medical first responders to natural disasters in China: a cluster randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of a system based psychological first aid (PFA) training programme for emergency medical first responders in China. DESIGN: Parallel-group, assessor-blinded, cluster randomised controlled trial. SETTING: 42 clusters of health workers from various health facilities in China. PARTICIPANTS: 1399 health workers who provide emergency service for survivors of disasters. INTERVENTIONS: One-day system based PFA training programme (PFA) or training as usual (TAU). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the PFA skills, knowledge and attitude (SKA-PFA) score at 2 months postintervention. Secondary outcomes included post-traumatic growth, self-efficacy and professional quality of life. RESULTS: The intervention group (n=690) had significantly higher SKA-PFA scores than the control group (n=709) at 2 months postintervention (adjusted mean difference=4.44; 95% CI 1.17 to 7.52; p=0.007; Cohen's d=0.35). The intervention group also had higher scores on post-traumatic growth (p=0.113, d=0.24), self-efficacy (p=0.032, d=0.20) and professional quality of life (p=0.281, d=0.04). CONCLUSIONS: The system based PFA training programme was more effective than the TAU in enhancing the PFA knowledge and skills of the emergency medical first responders and in increasing their competence to provide emergency service for survivors in China. TRIAL REGISTRATION NUMBER: ChiCTR2200060464.

Acupuncture for generalized anxiety disorder: a study protocol for a randomized controlled trial.

During the COVID-19 outbreak, there was a sharp increase in generalized anxiety disorder (GAD). Acupuncture therapy has the advantages of accurate clinical efficacy, safety and reliability, few adverse reactions, and no dependence, and is gradually becoming one of the emerging therapies for treating GAD. We present a study protocol for a randomized clinical trial with the aim of exploring the mechanism of brain plasticity in patients with GAD and evaluate the effectiveness and reliability of acupuncture treatment. Transcranial magnetic stimulation (TMS) will be used to assess cortical excitability in GAD patients and healthy people. Sixty-six GAD patients meeting the inclusion criteria will be randomly divided into two groups: TA group, (treatment with acupuncture and basic western medicine treatment) and SA group (sham acupuncture and basic western medicine treatment). Twenty healthy people will be recruited as the control group (HC). The parameters that will be evaluated are amplitude of motor evoked potentials (MEPs), cortical resting period (CSP), resting motor threshold (RMT), and Hamilton Anxiety Scale (HAMA) score. Secondary results will include blood analysis of γ-aminobutyric acid (GABA), glutamate (Glu), glutamine (Gln), serotonin (5-HT), and brain-derived nerve growth factor (BDNF). Outcomes will be assessed at baseline and after the intervention (week 8). This study protocol is the first clinical trial designed to detect differences in cerebral cortical excitability between healthy subjects and patients with GAD, and the comparison of clinical efficacy and reliability before and after acupuncture intervention is also one of the main contents of the protocol. We hope to find a suitable non-pharmacological alternative treatment for patients with GAD.

Clinical study on the difference in intestinal microecology between patients with preeclampsia and pregnant women at different stages of pregnancy.

Objective: To explore the difference in intestinal microecology between patients with preeclampsia and pregnant women at different stages of pregnancy. Methods: From January 2020 to January 2022, clinical data, including blood routine, lipid profile, and renal function indicators, were gathered from a cohort consisting of 5 cases of preeclampsia and 34 cases of non-preeclampsia. The non-preeclampsia group was further categorized into 6 cases in the First trimester, 13 cases in the Second trimester, and 15 cases in the Third trimester. The data collection took place at the Obstetrics Department of the Maternal and Child Health Hospital of Hubei Province. Additionally, fecal samples were obtained from each subject for 16S rDNA gene sequencing and subsequent analysis. The clinical data and composition characteristics of the gut microbiota in each group were analyzed, and the correlation between gut microbiota and clinical data was analyzed by the Spearman correlation analysis method. Results: In comparison to pregnant women without preeclampsia, preeclampsia patients exhibited a statistically significant elevation in blood routine parameters (WBC, N, L, and PLT count), a rise in lipid-related indicators (TC, TG, and LDL-C levels), a reduction in HDL-C levels, and an increase in renal function-related indicators (Cr, BUN, UA and Pro levels). Compared with non-preeclampsia pregnant women, preeclampsia women exhibited an augmented diversity of gut microbiota. Differences in gut microbiota composition between the two groups were observed at the gate and genus levels. Moreover, there are significant differences in the composition of gut microbiota between the preeclampsia group and the third-trimester group in terms of genus and species, and this difference is mainly caused by Prevotella and s_ Bacteroides_ Uniformis and Ruminococcus_ bromii. In addition, actinobacteria, bifidobacterium at the genus level, and Ruminococcus_bromii at the species level are positively correlated with clinically relevant indicators (excluding HDL-C). Conclusion: There are significant differences in gut microbiota between preeclampsia pregnant women and late pregnancy pregnant without preeclampsia, including Prevotella and Bacteroides_ Uniformis, and Ruminococcus_ bromii. In addition, these differential bacteria are correlated with most clinical indicators. However, additional comprehensive analysis is required to ascertain the functional correlation between these bacteria and clinical indicators.

Pollen-expressed RLCKs control pollen tube burst.

In angiosperms, the pollen tube enters the receptive synergid cell, where it ruptures to release its cytoplasm along with two sperm cells. This interaction is complex, and the exact signal transducers that trigger the bursting of pollen tubes are not well understood. In this study, we identify three homologous receptor-like cytoplasmic kinases (RLCKs) expressed in pollen tubes of Arabidopsis, Delayed Burst 1/2/3 (DEB1/2/3), which play a crucial role in this process. These genes produce proteins localized on the plasma membrane, and their knockout causes delayed pollen tube burst and entrance of additional pollen tubes into the embryo sac due to fertilization recovery. We show that DEBs interact with the Ca2+ pump ACA9, influencing the dynamics of cytoplasmic Ca2+ in pollen tubes through phosphorylation. These results highlight the importance of DEBs as key signal transducers and the critical function of the DEB-ACA9 axis in timely pollen tube burst in synergids.

Estrogen Induces LCAT to Maintain Cholesterol Homeostasis and Suppress Hepatocellular Carcinoma Development.

Hepatocellular carcinoma (HCC) is an aggressive disease that occurs predominantly in men. Estrogen elicits protective effects against HCC development. Elucidation of the estrogen-regulated biological processes that suppress HCC could lead to improved prevention and treatment strategies. Here, we performed transcriptomic analyses on mouse and human liver cancer and identified lecithin cholesterol acyltransferase (LCAT) as the most highly estrogen-upregulated gene and a biomarker of favorable prognosis. LCAT upregulation inhibited HCC in vitro and in vivo and mediated estrogen-induced suppression of HCC in an ESR1-dependent manner. LCAT facilitated high-density lipoprotein cholesterol production and uptake via the LDLR and SCARB1 pathways. Consistently, high HDL-C levels corresponded to a favorable prognosis in HCC patients. The enhanced HDL-C absorption induced by LCAT impaired SREBP2 maturation, which ultimately suppressed cholesterol biosynthesis and dampened HCC cell proliferation. HDL-C alone inhibited HCC growth comparably to the cholesterol-lowering drug lovastatin, and SREBF2 overexpression abolished the inhibitory activity of LCAT. Clinical observations and cross-analyses of multiple databases confirmed the correlation of elevated LCAT and HDL-C levels to reduced cholesterol synthesis and improved HCC patient prognosis. Furthermore, LCAT deficiency mimicked whereas LCAT overexpression abrogated the tumor growth-promoting effects of ovariectomy in HCC-bearing female mice. Most importantly, HDL-C and LCAT delayed the development of subcutaneous tumors in nude mice, and HDL-C synergized with lenvatinib to eradicate orthotopic liver tumors. Collectively, this study reveals that estrogen upregulates LCAT to maintain cholesterol homeostasis and to dampen hepatocarcinogenesis. LCAT and HDL-C represent potential prognostic and therapeutic biomarkers for targeting cholesterol homeostasis as a strategy for treating HCC. Significance: Estrogen mediates the sex differences in hepatocellular carcinoma development by reducing cholesterol biosynthesis through activation of an LCAT/HDL-C axis, providing strategies for improving liver cancer prevention, prognosis, and treatment.