Dissecting the shared genetic landscape of anxiety, depression, and schizophrenia.

BACKGROUND: Numerous studies highlight the genetic underpinnings of mental disorders comorbidity, particularly in anxiety, depression, and schizophrenia. However, their shared genetic loci are not well understood. Our study employs Mendelian randomization (MR) and colocalization analyses, alongside multi-omics data, to uncover potential genetic targets for these conditions, thereby informing therapeutic and drug development strategies. METHODS: We utilized the Consortium for Linkage Disequilibrium Score Regression (LDSC) and Mendelian Randomization (MR) analysis to investigate genetic correlations among anxiety, depression, and schizophrenia. Utilizing GTEx V8 eQTL and deCODE Genetics pQTL data, we performed a three-step summary-data-based Mendelian randomization (SMR) and protein-protein interaction analysis. This helped assess causal and comorbid loci for these disorders and determine if identified loci share coincidental variations with psychiatric diseases. Additionally, phenome-wide association studies, drug prediction, and molecular docking validated potential drug targets. RESULTS: We found genetic correlations between anxiety, depression, and schizophrenia, and under a meta-analysis of MR from multiple databases, the causal relationships among these disorders are supported. Based on this, three-step SMR and colocalization analyses identified ITIH3 and CCS as being related to the risk of developing depression, while CTSS and DNPH1 are related to the onset of schizophrenia. BTN3A1, PSMB4, and TIMP4 were identified as comorbidity loci for both disorders. Molecules that could not be determined through colocalization analysis were also presented. Drug prediction and molecular docking showed that some drugs and proteins have good binding affinity and available structural data. CONCLUSIONS: Our study indicates genetic correlations and shared risk loci between anxiety, depression, and schizophrenia. These findings offer insights into the underlying mechanisms of their comorbidities and aid in drug development.

Telitacicept Treatment Refractory Lupus Nephritis: A Case Report.

Introduction: Refractory lupus nephritis (LN) causes kidney disease progression and increases the risk of loss of renal function. Due to the high specificity and few side effects of biological agents, they are recommended for the treatment of systemic lupus erythematosus. There are few data on telitacicept for the treatment of refractory LN. Case Presentation: Here, we report the efficacy and safety of telitacicept in the treatment of refractory LN in a 25-year-old female patient. This patient with refractory lupus developed Pneumocystis jirovecii pneumonia while using multitargeted therapy, and the patient's urine protein was rapidly relieved after telitacicept combination with low-dose mycophenolate mofetil (MMF). Conclusion: This result suggests that telitacicept has a positive effect on refractory LN with no significant side effects. Further reports and a registry are necessary to confirm that telitacicept with low-dose MMF should be preferred in refractory LN.

Recurrent neural network-based simultaneous cardiac T1, T2, and T1ρ mapping.

The purpose of the current study was to explore the feasibility of training a deep neural network to accelerate the process of generating T1, T2, and T1ρ maps for a recently proposed free-breathing cardiac multiparametric mapping technique, where a recurrent neural network (RNN) was utilized to exploit the temporal correlation among the multicontrast images. The RNN-based model was developed for rapid and accurate T1, T2, and T1ρ estimation. Bloch simulation was performed to simulate a dataset of more than 10 million signals and time correspondences with different noise levels for network training. The proposed RNN-based method was compared with a dictionary-matching method and a conventional mapping method to evaluate the model's effectiveness in phantom and in vivo studies at 3 T, respectively. In phantom studies, the RNN-based method and the dictionary-matching method achieved similar accuracy and precision in T1, T2, and T1ρ estimations. In in vivo studies, the estimated T1, T2, and T1ρ values obtained by the two methods achieved similar accuracy and precision for 10 healthy volunteers (T1: 1228.70 ± 53.80 vs. 1228.34 ± 52.91 ms, p > 0.1; T2: 40.70 ± 2.89 vs. 41.19 ± 2.91 ms, p > 0.1; T1ρ: 45.09 ± 4.47 vs. 45.23 ± 4.65 ms, p > 0.1). The RNN-based method can generate cardiac multiparameter quantitative maps simultaneously in just 2 s, achieving 60-fold acceleration compared with the dictionary-matching method. The RNN-accelerated method offers an almost instantaneous approach for reconstructing accurate T1, T2, and T1ρ maps, being much more efficient than the dictionary-matching method for the free-breathing multiparametric cardiac mapping technique, which may pave the way for inline mapping in clinical applications.

Real-world effectiveness of seasonal influenza vaccination and age as effect modifier: A systematic review, meta-analysis and meta-regression of test-negative design studies.

BACKGROUND: Under the global risk of epidemic rebound of influenza after COVID-19 outbreak, the study aimed to provide a comprehensive evaluation of the seasonal influenza vaccine effectiveness (IVE) and to explore the potential effect modifiers. METHODS: We searched for test-negative design studies with IVE estimates published between January 1, 2017 and December 31, 2022. We estimated pooled IVE using random-effects meta-analysis, and conducted meta-regression with study site, age, sex and comorbidity as explanatory variables. RESULTS: We identified 2429 publications and included 191 in the meta-analysis. The pooled IVE was 41.4 % (95 % CI: 39.2-43.5 %) against any influenza. For specific strains, the IVE was 55.4 % (95 % CI: 52.7-58.1 %) against A/H1N1, 26.8 % (95 % CI: 23.5-29.9 %) against A/H3N2, 47.2 % (95 % CI: 38.1-54.9 %) against B/Yamagata, and 40.6 % (95 % CI: 23.7-53.7 %) against B/Victoria, and the effectiveness against A/H3N2 was significantly lower than A/H1N1 (p < 0.0001) and B/Yamagata (p < 0.0001). The pooled IVE was 39.2 % (95 % CI: 36.5-41.9 %) in preventing influenza-associated outpatient visit and 43.7 % (95 % CI: 39.7-47.4 %) in preventing influenza-related hospitalization. The IVE against any influenza was 48.6 % (95 % CI: 44.7-52.2 %) for children aged < 18 years, 36.7 % (95 % CI: 31.9-41.1 %) for adults aged 18-64 years, and 30.6 % (95 % CI: 26.2-34.8 %) for elderly aged ≥65 years. Meta-regression revealed that the IVE was associated with the average age of study participants, in which both young adults [relative odds ratio (ROR) = 1.225, 95 % confidence interval (CI): 1.099-1.365, p = 0.0002] and elderly (ROR = 1.245, 95 % CI: 1.083-1.431, p = 0.002) manifested a significantly decreased effectiveness compared with children. CONCLUSIONS: Influenza vaccines provided moderate protection against laboratory-confirmed influenza and related outpatient visit and hospitalization. However, the effectiveness may vary substantially by virus type and age group, suggesting the necessity to tailor vaccination strategies especially for older individuals and against the A/H3N2 strain, and to promote annual immunization and annual analysis of vaccine effectiveness.

The role of platelets in sepsis: A review.

Sepsis, a life-threatening condition characterized by organ dysfunction, results from a complex series of pathophysiological mechanisms including immune dysfunction, an uncontrolled inflammatory response, and coagulation abnormalities. It is a major contributor to global mortality and severe disease development. Platelets, abundant in the circulatory system, are sensitive to changes in the body's internal environment and are among the first cells to respond to dysregulated pro-inflammatory and pro-coagulant reactions at the onset of sepsis. In the initial stages of sepsis, the coagulation cascade, inflammatory response, and endothelial tissue damage perpetually trigger platelet activation. These activated platelets then engage in complex inflammatory and immune reactions, potentially leading to organ dysfunction. Therefore, further research is essential to fully understand the role of platelets in sepsis pathology and to develop effective therapeutic strategies targeting the associated pathogenic pathways. This review delves into the involvement of platelets in sepsis and briefly outlines the clinical applications of associated biomarkers.

Assessing the causal relationship between COVID-19 and post-COVID-19 syndrome: A Mendelian randomisation study.

Background: In the aftermath of the coronavirus disease 2019 (COVID-19) pandemic, we sought to explore the causal association between COVID-19 and 17 prevalent post-COVID-19 syndrome (PCS) symptoms using Mendelian randomisation (MR) methodology. Methods: We used 22 extensive genome-wide association study (GWAS) data sets, incorporating genetic variants as instrumental variables. Univariate Mendelian randomisation (UVMR) analyses involved 15 single nucleotide polymorphisms (SNPs) for COVID-19 patients, 33 for hospitalised COVID-19 patients, and 29 for patients with severe respiratory symptoms due to COVID-19. Furthermore, we further used multivariable Mendelian randomisation (MVMR) analyses based on 93 SNPs for COVID-19 patients, 105 for hospitalised COVID-19 patients, and 99 for patients with severe respiratory symptoms due to COVID-19. With these analyses, we aimed to assess the causal associations between varying levels of COVID-19 infection and 17 prevalent PCS symptoms while accounting for the influence of educational and income levels. Results: UVMR analysis identified potential causal effects of COVID-19 genetic susceptibility on myalgia and pain in various regions. Hospitalised COVID-19 was potentially linked to erectile dysfunction and alopecia areata. Very severe respiratory confirmed patients exhibited increased pain and tobacco use. Meanwhile, the MVMR analysis demonstrated a potential causal link between hospitalised COVID-19 and heart arrhythmia, and a protective effect of COVID-19 on tobacco use after adjusting for educational and income levels. Conclusions: Our MR analysis provides compelling evidence of causal associations between genetic susceptibility to COVID-19 and specific PCS symptoms, in which educational and income levels play a mediating role. These findings shed light on PCS pathogenesis and underscore the importance of considering social factors in its management. Tailored interventions and policies are crucial for PCS-affected individuals' well-being. Further research is needed to explore the impact of social determinants on COVID-19 patients and the wider population.

Mitigation of Sepsis-Induced Acute Lung Injury by BMSC-Derived Exosomal miR-125b-5p Through STAT3-Mediated Suppression of Macrophage Pyroptosis.

Introduction: Sepsis is a syndrome characterized by high morbidity and mortality rates. One of its most severe complications is acute lung injury, which exhibits a multitude of clinical and biological features, including macrophage pyroptosis. This study investigates the regulatory effects of exosomes derived from Bone Marrow-Derived Mesenchymal Stem Cells (BMSCs) on sepsis-associated acute lung injury (ALI) and explores the potential mechanisms mediated by exosomal miRNAs. Methods: Exosomes were isolated from primary BMSCs of adult C57BL/6J mice using differential centrifugation. Their uptake and distribution in both in vitro and in vivo contexts were validated. Key sepsis-associated hub gene signal transducer and activator of transcription 3 (STAT3) and its upstream non-coding miR-125b-5p were elucidated through a combination of bioinformatics, machine learning, and miRNA sequencing. Subsequently, the therapeutic potential of BMSC-derived exosomes in alleviating sepsis-induced acute lung injury was substantiated. Moreover, the functionalities of miR-125b-5p and STAT3 were corroborated through miR-125b-5p inhibitor and STAT3 agonist interventions, employing gain and loss-of-function strategies both in vitro and in vivo. Finally, a dual-luciferase reporter assay reaffirmed the interaction between miR-125b-5p and STAT3. Results: We isolated exosomes from primary BMSCs and confirmed their accumulation in the mouse lung as well as their uptake by macrophages in vitro. This study identified the pivotal sepsis-associated hub gene STAT3 and demonstrated that exosomes derived from BMSCs can target STAT3, thereby inhibiting macrophage pyroptosis. MiR-125b-5p inhibition experiments showed that exosomes mitigate macrophage pyroptosis and lung injury by delivering miR-125b-5p. STAT3 overexpression experiments validated that miR-125b-5p reduces macrophage pyroptosis and lung injury by suppressing STAT3. Furthermore, a dual-luciferase reporter assay confirmed the binding interaction between miR-125b-5p and STAT3. Conclusion: Exosomes derived from BMSCs, serving as carriers for delivering miR-125b-5p, can downregulate STAT3, thereby inhibiting macrophage pyroptosis and alleviating sepsis-associated ALI. These significant findings provide valuable insights into the potential development of ALI therapies centred around exosomes derived from BMSC.

Validation of metagenomic next-generation sequencing of bronchoalveolar lavage fluid for diagnosis of suspected pulmonary infections in patients with systemic autoimmune rheumatic diseases receiving immunosuppressant therapy.

Background: The accuracy and sensitivity of conventional microbiological tests (CMTs) are insufficient to identify opportunistic pathogens in patients with systemic autoimmune rheumatic diseases (SARDs). The study aimed to assess the usefulness of metagenomic next-generation sequencing (mNGS) vs. CMTs for the diagnosis of pulmonary infections in patients with SARDs receiving immunosuppressant therapy. Methods: The medical records of 40 patients with pulmonary infections and SARDs treated with immunosuppressants or corticosteroids were reviewed retrospectively. Bronchoalveolar lavage fluid (BALF) samples were collected from all patients and examined by mNGS and CMTs. Diagnostic values of the CMTs and mNGS were compared with the clinical composite diagnosis as the reference standard. Results: Of the 40 patients included for analysis, 37 (92.5%) were diagnosed with pulmonary infections and 3 (7.5%) with non-infectious diseases, of which two were considered primary diseases and one an asthma attack. In total, 15 pathogens (7 bacteria, 5 fungi, and 3 viruses) were detected by CMTs as compared to 58 (36 bacteria, 12 fungi, and 10 viruses) by mNGS. Diagnostic accuracy of mNGS was superior to that of the CMTs for the detection of co-infections with bacteria and fungi (95 vs. 53%, respectively, p < 0.01), and for the detection of single infections with fungi (97.5 vs. 55%, respectively, p < 0.01). Of the 31 patients diagnosed with co-infections, 4 (12.9%) were positive for two pathogens and 27 (87.1%) for three or more. The detection rate of co-infection was significantly higher for mNGS than CMTs (95 vs. 16%, respectively, p < 0.01). Conclusion: The accuracy of mNGS was superior to that of the CMTs for the diagnosis of pulmonary infections in patients with SARDs treated with immunosuppressants. The rapid diagnosis by mNGS can ensure timely adjustment of treatment regimens to improve diagnosis and outcomes.

Adverse effects of 21 antidepressants on sleep during acute-phase treatment in major depressive disorder: a systemic review and dose-effect network meta-analysis.

STUDY OBJECTIVES: Sleep-related adverse effects during acute treatment with antidepressants undermine adherence and impede remission. We aimed to address subtypes of sleep-related adverse effects and depict the relationship between dose and sleep-related adverse events. METHODS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science for double-blind randomized controlled trials of depression published before April 30th, 2023. Eligible studies reporting sleep-related adverse effects during short-term monotherapy were included. The odds ratios (ORs) for sleep-related adverse effects were addressed with network meta-analysis. A Bayesian approach was used to depict the dose-effect relationship. Heterogeneity among studies was assessed using the τ2 and I2 statistics. Sensitivity analyses were performed without studies featuring high risk of bias. RESULTS: Studies with 64 696 patients were examined from 216 trials. Compared to placebo, 13 antidepressants showed higher ORs for somnolence, of which fluvoxamine (OR = 6.32; 95% CI: 3.56 to 11.21) ranked the top. Eleven had higher risks for insomnia, reboxetine ranked the top (OR = 3.47; 95% CI: 2.77 to 4.36). The dose-effect relationships curves between somnolence or insomnia and dose included linear shape, inverted U-shape, and other shapes. There was no significant heterogeneity among individual studies. The quality of evidence for results in network meta-analyses was rated as very low to moderate by Grading of Recommendations Assessment, Development, and Evaluation. CONCLUSIONS: Most antidepressants had higher risks for insomnia or somnolence than placebo. The diverse relationship curves between somnolence or insomnia and dose of antidepressants can guide clinicians to adjust the doses. These findings suggest clinicians pay more attention to sleep-related adverse effects during acute treatment with antidepressants.

Tumor-stroma ratio predicts prognosis and PD-L1 expression in hepatocellular carcinoma.

BACKGROUND: With the in-depth research on the tumor microenvironment, the tumor stroma is considered to play a leading role in malignant tumor behavior, and PD-L1 is also related to the tumor stroma. The tumor-stroma ratio (TSR) has been regarded as a novel prognostic factor in many cancers. Our study aims to assess the TSR and PD-L1 clinical value in hepatocellular carcinoma (HCC) patients. METHODS: Ninety-five patients who were diagnosed with HCC were included in our study. TSR was estimated on HCC specimen hematoxylin-eosin staining (HE) sections, and the optimal TSR cut-off value was determined by receiver operating characteristic (ROC) curves. The correlation between the TSR and clinicopathologic features was also calculated. Immunohistochemistry (IHC) staining was also carried out to analyze the PD-L1 expression level in HCCs. RESULTS: The optimal TSR cut-off value was 0.525. The median OS of the stroma-high and stroma-low groups was 27 and 36 months, respectively. The median RFS of the stroma-high and stroma-low groups was 14.5 and 27 months, respectively. In the Cox multivariate analysis, the TSR was an independent prognostic factor for HCC overall survival (OS) and recurrence-free survival (RFS) in patients who underwent liver resection. IHC staining revealed TSR-high HCC samples with high PD-L1-positive cell expression. CONCLUSIONS: Our results suggest that the TSR can predict the prognosis of HCC patients who underwent liver resection. The TSR is related to PD-L1 expression and may be a therapeutic target that can dramatically improve HCC patients' clinical outcomes.

Mangiferin inhibits chronic stress-induced tumor growth in colorectal liver metastases via WAVE2 signaling pathway.

Background: Evidence indicates that chronic stress promotes progression of colorectal liver metastases (CLM). Mangiferin is the active chemical constituent of the rhizomes of Anemarrhena asphodeloides Bunge. Mangiferin (MGF) exerts anti-inflammatory, anti-proliferative, anti-angiogenic, anti-fibrotic and antioxidant effects in a variety of cancers. Its mechanism in chronic stress and tumor growth is still poorly understood. Methods: To investigate the effects of MGF on the CLM and tumor-associated depression, activated hepatic stellate cells (a-HSCs), HT-29 CRC cells, were used in chronic unpredictable mild stress (CUMS) of tumor-bearing models. Potential antidepressant activity was determined by FST, TST, SIT and serum cytokine (IL-6, IL-18 and TNF-α) examination. Downstream signaling molecules were detected by Western blot, immunohistochemistry and fluorescence microscopy. Results: CUMS induced depression behavior and depression-related cytokines and promoted tumor growth in CLM. MGF-treated mice significantly improved chronic stress behaviors by reducing depression-related cytokines. In addition, MGF treatment inhibits WAVE2 signaling pathway, leading to TGF-ß1 induced HSC inhibition, thereby reducing depressive behavior and tumor growth in CLM. Conclusion: MGF can alleviate CUMS induced tumor growth and the treatment of CLM patients with MGF may be beneficial.

THE IL-33/ST2 AXIS PROMOTES ACUTE RESPIRATORY DISTRESS SYNDROME BY NATURAL KILLER T CELLS.

ABSTRACT: Acute respiratory distress syndrome (ARDS) is characterized by uncontrolled inflammation, which manifests as leukocyte infiltration and lung injury. However, the molecules that initiate this infiltration remain incompletely understood. We evaluated the effect of the nuclear alarmin IL-33 on lung damage and the immune response in LPS-induced lung injury. We established a LPS-induced lung injury mouse model. We used genetically engineered mice to investigate the relationship among the IL-33/ST2 axis, NKT cells, and ARDS. We found that IL-33 was localized to the nucleus in alveolar epithelial cells, from which it was released 1 h after ARDS induction in wild-type (WT) mice. Mice lacking IL-33 (IL-33 - / - ) or ST2 (ST2 - / - ) exhibited reduced neutrophil infiltration, alveolar capillary leakage, and lung injury in ARDS compared with WT mice. This protection was associated with decreased lung recruitment and activation of invariant nature killer (iNKT) cells and activation of traditional T cells. Then, we validated that iNKT cells were deleterious in ARDS in CD1d - / - and Vα14Τg mice. Compared with WT mice, Vα14Τg mice exhibited increased lung injury in ARDS, and the CD1d - / - mice showed outcomes opposite those of the Vα14Τg mice. Furthermore, we administered a neutralizing anti-ST2 antibody to LPS-treated WT and Vα14Τg mice 1 h before LPS administration. We found that IL-33 promoted inflammation through NKT cells in ARDS. In summary, our results demonstrated that the IL-33/ST2 axis promotes the early uncontrolled inflammatory response in ARDS by activating and recruiting iNKT cells. Therefore, IL-33 and NKT cells may be therapeutic target molecules and immune cells, respectively, in early ARDS cytokine storms.

Case Report: Acute Intoxication from Phosphine Inhalation.

Aluminum phosphide is a highly effective insecticide for fumigation in granaries and is often used in rural grain storage. However, people's awareness of its toxicity is not strong. A case of acute inhalation toxicity of phosphine caused by the use of aluminum phosphide to fumigate a granary is reported here. The case presented with aspiration pneumonia and acute left heart failure. The patient was cured using comprehensive life support treatment, including respiratory support, antiarrhythmic treatment, and blood pressure maintenance with vasoactive drugs. There is no specific antidote for phosphine poisoning at present, and the comprehensive application of restricted fluid resuscitation, high-dose glucocorticoid shock, vasoactive drugs and bedside hemofiltration is significant in improving the prognosis of patients. It is also important to remind people to pay attention to their own protection in the process of using aluminum phosphide.

Immunogenicity and reactogenicity of heterologous immunization schedules with COVID-19 vaccines: a systematic review and network meta-analysis.

BACKGROUND: Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules. METHODS: Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model. RESULTS: In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons. CONCLUSIONS: Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted. REGISTRATION: PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42021278149.

Chromosome 12 Open Reading Frame 49 Promotes Tumor Growth and Predicts Poor Prognosis in Colorectal Cancer.

BACKGROUND AND AIMS: Little is known about the role of chromosome 12 open reading frame 49 (C12ORF49)-induced metabolic signal transduction in tumor growth. We investigated the relationship between C12ORF49 expression and prognosis in colorectal cancer (CRC) patients. METHODS: C12ORF49 protein expression was measured in CRC tissues by Western blot and immunohistochemistry staining. Knock out of C12ORF49 in CRC cells was then performed, and the role of C12ORF49 in CRC cell proliferation and growth was examined. The expression of C12ORF49 in CRC was analyzed in Gene Expression Profiling Interactive Analysis (GEPIA) databases. A prognosis model with 11 C12ORF49-associated genes (CAGs) was generated by TCGA databases. RESULTS: C12ORF49 expression was significantly higher in CRC tumor tissue than in non-tumor tissue. Furthermore, in vitro and in vivo loss-of-function experiments, showed that C12ORF49 plays critical roles in promoting tumor cell growth. There was a significant correlation between C12ORF49 protein and the presence of tumor necrosis. C12ORF49 is critical for its interaction with SREBF1, TMEM41A, and S1PR3 in the poor prognosis of CRC. CONCLUSIONS: Our results suggest that C12ORF49 plays a key role in CRC tumor growth.

Impact of pulmonary hypertension on arteriovenous fistula failure of hemodialysis patients: A 10 years follow-up cohort study.

BACKGROUND: Pulmonary hypertension (PH) is common in patients with end-stage renal disease (ESRD). Arteriovenous fistulas (AVF) creation may involve in the pathogenesis of PH. The aim of this study was to explore the impact of PH after AVF creation on the AVF failure rate in maintenance hemodialysis (MHD) patients. METHODS: From January 1, 2009, to January 1, 2019, we retrospectively collected data of 578 MHD patients in Guangdong Provincial People's Hospital Blood Purification Center, China. Patients were followed-up until AVF failure or death or May 25, 2020. According to the systolic pulmonary artery pressure (SPAP) within 1 year after the establishment of AVF, the MHD patients were divided into three groups: SPAP ⩽ 35 mmHg, 35 < SPAP < 45 mmHg, SPAP ⩾ 45 mmHg. The primary outcome was AVF failure defined as AVF cannot complete hemodialysis. The secondary outcomes were all-cause mortality. RESULTS: A total of 578 patients were analyzed. The average age was 60.66 ± 15.34 years (58.1% men). Of these, 26.1% of patients were reported PH. The SPAP exhibited a left-skewed nonparametric distribution and the overall SPAP after the creation of AVF was 39.00 (29.00-52.00) mmHg. The median follow-up was 5.8 (5.5-6.3) years. Overall, 12.8% (74/578) patients were reported AVF failure events. There was no significant difference in AVF failure rate among three groups (p = 0.070). A total of 111 (19.2%) died during the follow-up period. Compared with the SPAP ⩽35 mmHg group, only the all-cause death rate significantly increased in MHD patients with PH (p < 0.001). CONCLUSIONS: The secondary pulmonary hypertension after AVF creation did not increase the risk of AVF failure in MHD patients, but significantly increased the risk of mortality for this portion of the patients. Future larger sample sizes, multi-center, and prospective trials are needed to make sure which type of access will benefit on their survival for MHD patients with SPAP ⩾35 mmHg.

Toxic Encephalopathy and Methemoglobinemia after 5-Amino-2-(trifluoromethyl)pyridine Poisoning.

The aromatic amino compound 5-amino-2-(trifluoromethyl)pyridine acts as an intermediate in the synthesis of pharmaceutical products. However, the toxicity profile of this compound is sparse and no related poisoning events have been reported. Here, we report the case of a 35-year-old man who inhaled 5-amino-2-(trifluoromethyl)pyridine at work. After inhalation, the patient rapidly developed symptoms such as dizziness, fatigue, nausea, vomiting, chest tightness, and loss of consciousness. After admission, methemoglobinemia, hemolytic anemia, acute renal failure, and toxic encephalopathy occurred. Symptoms improved significantly after intravenous treatment with a low dose of methylene blue. This revealed that 5-amino-2-(trifluoromethyl)pyridine is toxic to the human body and can be absorbed through the respiratory tract, resulting in methemoglobinemia and toxic encephalopathy; thus, caution should be taken in industrial production.

The Mediation Role of Self-Control in the Association of Self-Efficacy and Physical Activity in College Students.

Global COVID-19 lockdown measures have led to an apparent decrease in physical activity. This study aimed to explore the explanatory function of self-control's mediating role between self-efficacy and physical activity among college students. The analysis used the data of 1627 university students (aged 19.41 ± 0.66, range 17-28, 40.5% males) at Shanghai Jiao Tong University. Self-efficacy, self-control, and physical activity were tested, respectively, by the general self-efficacy scale, the new brief self-control scale, and the International Physical Activity Questionnaire (IPAQ) scale, which were analyzed by SPSS software. Correlation analysis showed that self-efficacy, self-control, and physical activity were related in pairs. Comparing the two dimensions of self-control, we found that self-discipline mediated the relationship between self-efficacy and PA, and impulse control did not mediate the relationship. Regarding the gender difference according to multi-group analysis, findings showed that females need higher self-discipline from the path of self-efficacy to physical activity improvement than males.

Reversible Splenial Lesion Syndrome (RESLES) after Nitrous Oxide Abuse: A Case Report.

BACKGROUND: Reversible splenial-lesion syndrome (RESLES) is a relatively rare and underrecognized clinical-imaging syndrome involving the splenium of the corpus callosum (SCC). RESLES can be caused by various etiologies. CASE DESCRIPTION: An 18-year-old man with no previous history of neurological or psychiatric disorders presented to our hospital with headache, intermittent blurred vision, and limb weakness after 150 days of recreational nitrous-oxide abuse. The patient's serum vitamin B12 concentration was normal, and magnetic-resonance imaging (MRI) examination revealed isointensity on T1-weighted imaging (T1WI) of the corpus callosum and high signal intensity on T2WI, T2FLAIR, and diffusion-weighted MRI (DWI); thus, a diagnosis of RESLES was established. The patient received 0.5 mg of mecobalamin daily and nitrous oxide was discontinued. After 4 weeks, the patient's symptoms disappeared and the imaging examination revealed normal findings. CONCLUSION: We report for the first time a case of headache, blurred vision, and hallucination caused by RESLES associated with nitrous-oxide abuse. In cases of headaches and hallucinations of unknown etiology, the possibility of RESLES caused by nitrous oxide abuse should be considered.

The role of lung macrophages in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is an acute and diffuse inflammatory lung injury in a short time, one of the common severe manifestations of the respiratory system that endangers human life and health. As an innate immune cell, macrophages play a key role in the inflammatory response. For a long time, the role of pulmonary macrophages in ARDS has tended to revolve around the polarization of M1/M2. However, with the development of single-cell RNA sequencing, fate mapping, metabolomics, and other new technologies, a deeper understanding of the development process, classification, and function of macrophages in the lung are acquired. Here, we discuss the function of pulmonary macrophages in ARDS from the two dimensions of anatomical location and cell origin and describe the effects of cell metabolism and intercellular interaction on the function of macrophages. Besides, we explore the treatments for targeting macrophages, such as enhancing macrophage phagocytosis, regulating macrophage recruitment, and macrophage death. Considering the differences in responsiveness of different research groups to these treatments and the tremendous dynamic changes in the gene expression of monocyte/macrophage, we discussed the possibility of characterizing the gene expression of monocyte/macrophage as the biomarkers. We hope that this review will provide new insight into pulmonary macrophage function and therapeutic targets of ARDS.