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Abstract 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.

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.

Background Secondary hyperparathyroidism (SHPT) is a prevalent chronic complication in patients undergoing hemodialysis. Parathyroidectomy (PTX) is crucial for reducing mortality and improving the prognosis in the treatment of refractory hyperparathyroidism. However, it is often associated with a number of postoperative complications such as postoperative hypotension, hyperkalemia, and hungry bone syndrome. A previous study demonstrated that low blood pressure influences the patency of autogenous arteriovenous fistulas (AVF). Few studies have examined AVF dysfunction following PTX. This study aimed to identify and describe the risk variables associated with AVF dysfunction after PTX.Methods Cases of AVF dysfunction after PTX between 2015 and 2021 were studied. Four controls were identified for each patient and were matched for sex and age. Biochemical parameters and blood pressure of the patients before and after PTX were recorded. Risk factors for AVF dysfunction after PTX were identified using conditional logistic regression analysis.Results Sixteen patients and 64 controls were included in this study. Baseline demographic and laboratory data were compared. Patients in the AVF dysfunction group had lower levels of postoperative calcium than the controls. After surgery, calcium levels decreased more in patients with AVF dysfunction than in the control group. The decrease in systolic blood pressure (ΔSBP) after PTX was greater in the AVF dysfunction group than that in the control group. For each 1 mmHg increment in ΔSBP, the risk of AVF dysfunction after surgery increased by 11.6% (OR = 1.116, 95% CI, 1.005–1.239, p = .040). The likelihood of developing AVF dysfunction after surgery was twelvefold higher in diabetic patients than in non-diabetic patients (OR = 12.506, 95% CI, 1.113–140.492, p = .041). Among patients with ΔSBP > 5.8 mmHg after PTX, the AVF failure rate was significantly greater in patients with diabetes than in those without diabetes. Patients with a history of AVF failure had a nine-fold higher risk of developing AVF dysfunction (OR = 9.143, 95% CI, 1.151–72.627, p = .036). Serum albumin, hemoglobin, ΔiPTH, and age were not independent predictors of AVF dysfunction. The cutoff value for SBP was 5.8 mmHg, as determined by the Youden index of the receiver operating characteristic curve.Conclusion Decreased systolic blood pressure (ΔSBP) after PTX, diabetes, and AVF failure history were risk factors for AVF dysfunction following PTX in patients with SHPT. Diabetes patients with ΔSBP > 5.8 mmHg were more prone to AVF dysfunction after PTX.

Burnout, characterized by emotional and physical exhaustion, poses a significant challenge to adolescent athletes, particularly in high-intensity sports like basketball. Emotional Intelligence (EI) is the ability to manage emotions, which is negatively associated with burnout. Emotional labor, including strategies of surface acting (SA), deep acting (DA), and genuine expression (GE), plays a potentially key role in emotion management between EI and burnout for athletes. This study aims to investigate the relationship between EI and burnout, as well as the mediating role of emotional labor strategies among adolescent basketball players. Our cross-sectional study, conducted in youth sports schools in four different places in China, involved 260 basketball players. Results indicate a negative association between EI and burnout, with SA and GE emerging as significant mediators. SA was positively linked to burnout, while GE showed a negative association. These findings suggest that enhancing EI and managing emotional labor strategies are crucial for mitigating burnout and improving the well-being and performance of young athletes.

Urban street vitality has been a perennial focus within the domain of urban planning. This study examined spatial patterns of street vitality in the old city of Nanjing during working days and weekends using real-time user datasets (RTUDs). A spatial autoregressive model (SAM) and a multiscale geographically weighted regression (MGWR) model were employed to quantitatively assess the impact of various factors on street vitality and their spatial heterogeneity. This study revealed the following: (1) the distribution of street vitality in the old city of Nanjing exhibited a structure centered around Xinjiekou, with greater regularity and predictability in street vitality on working days than on weekends; (2) eight variables, such as traffic location, road density, and functional density, are positively associated with street vitality, whereas the green view index is negatively associated with street vitality, and commercial location benefits street vitality at weekends but detracts from street vitality on working days; and (3) the influence of variables such as traffic location and functional density on street vitality is contingent on their spatial position. Based on these results, this study provides new strategies to enhance the street vitality of old cities.

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.

Abstract 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.

Abstract. 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.

The herbicide paraquat is an agonist of Stromal Interaction Molecule 1 (STIM1), leading to extracellular calcium entry observed in epithelial-mesenchymal transition in alveolar cells during pulmonary fibrosis.

BackgroundThe 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.MethodsThe 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.ResultsOf 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

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-β1 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.

Paraquat is a non-selective contact herbicide that is absorbed through the digestive tract and skin and can cause multiple organ damage. The toxicokinetics of paraquat poisoning in specific patients are rarely reported. Case 1 was a 76-year-old man who intermittently immersed his perineum in diluted paraquat solution for 3 consecutive days because of eczema of the perineal skin. On admission, the patient’s scrotal skin was severely corroded and his blood paraquat concentration was 0.5 μg/mL. He developed severe kidney and lung damage after admission and died on Day 6 of admission. Case 2 was a 23-year-old woman who ingested paraquat during gestational week 36. Her initial blood paraquat concentration was 0.81 μg/mL. The patient refused hemoperfusion and a cesarean section. She birthed a baby girl 83 hours after ingesting paraquat. Paraquat concentrations in postnatal maternal blood, fetal blood, umbilical cord blood, and amniotic fluid were 0.19 μg/mL, 0.23 μg/mL, 0.20 μg/mL, and 0.47 μg/mL, respectively. The baby died within hours of birth and the mother died of refractory respiratory failure 2 days after delivery. This paper provides clues about paraquat toxicokinetics in specific patient types and indicates that paraquat can be absorbed through the scrotal skin and the placental barrier.

Background The study aimed to construct a clinical model based on preoperative data for predicting acute kidney injury (AKI) following cardiac surgery in patients with normal renal function. Methods A total of 22,348 consecutive patients with normal renal function undergoing cardiac surgery were enrolled. Among them, 15,701 were randomly selected for the training group and the remaining for the validation group. To develop a model visualized as a nomogram for predicting AKI, logistic regression was performed with variables selected using least absolute shrinkage and selection operator regression. The discrimination, calibration, and clinical value of the model were evaluated. Results The incidence of AKI was 25.2% in the training group. The new model consisted of nine preoperative variables, including age, male gender, left ventricular ejection fraction, hypertension, hemoglobin, uric acid, hypomagnesemia, and oral renin-angiotensin system inhibitor and non-steroidal anti-inflammatory drug within 1 week before surgery. The model had a good performance in the validation group. The discrimination was good with an area under the receiver operating characteristic curve of 0.740 (95% confidence interval, 0.726–0.753). The calibration plot indicated excellent agreement between the model prediction and actual observations. Decision curve analysis also showed that the model was clinically useful. Conclusions The new model was constructed based on nine easily available preoperative clinical data characteristics for predicting AKI following cardiac surgery in patients with normal kidney function, which may help treatment decision-making, and rational utilization of medical resources.

Background and PurposeCalcific Aortic Valve Disease (CAVD) is a crucial component of degenerative valvular disease in old age and with the increasing prevalence of the aging population. we hope that by modeling valvular osteogenesis and intervening with endoplasmic reticulum stress inhibitor TUDCA to observe the effect of endoplasmic reticulum stress on valve osteogenesisMethodsIn this study, rabbit heart valvular interstitial cells (VICs) were isolated and cultured. They treated with ox-LDL (Oxidized Low Density Lipoprotein) stimulation to establish a model of valvular osteogenic transformation. BMP2 (Bone Morphogenetic Protein 2), PERK (Protein kinase R-like endoplasmic reticulum kinase), CHOP (CCAAT/enhancer-binding protein homologous protein) and transcriptional regulatory factor ATF4 (Activating Transcription Factor 4 )were recorded after intervention with ER stress inhibitor TUDCA. The effects of er stress on valvular osteogenic transformation were analyzed.ResultAfter stimulation of VICs with ox-LDL, the expression levels of BMP2, PERK, CHOP, and ATF4 increased. However, TUDCA treatment can alleviate the increased expression levels of BMP2, PERK ATF4, and CHOP under ox-LDL stimulation to a certain extent.ConclusionThe endoplasmic reticulum stress signaling pathway is involved in ox-LDL-induced calcification of rabbit valve interstitial cells. Inhibition of endoplasmic reticulum stress using TUDCA can improve the progression of rabbit aortic valve calcification.

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 relationship between physical activity (PA) and physical fitness (PF) has been well established among college students. However, the impact of this relationship after 1 year of COVID-19 pandemic lockdown measures is unclear. This study aimed to test the relationship between PA and PF, exploring the trend across four years, the different components of PF related to PA, and their determinants, by analyzing specific items. A total of 1506 university students (19.48 ± 1.35 years old, 55.8% male) in years 1–4 at two comprehensive universities in Shanghai were recruited after one year of COVID restrictions and asked to complete the PF measurements and International Physical Activity Questionnaire (IPAQ Chinese Short version). The PA level is categorized into three types of intensity (low-moderate-high), and the level of PF is represented by the total test score of each item. Results show that PA was significantly positively correlated with PF; PA levels significantly predicted 1000m-run, 50m-sprint, and standing-long-jump in males, and 800m-sprint and sit-ups in females. Males predominantly had high-intensity PA, whereas females maintained moderate-intensity PA over four academic years. Meanwhile, PA and PF both trended downward as academic years increased in males and females, which could be attributed to a decline in high-intensity PA. The following two recommendations were obtained from the study: first, college students should engage in high-intensity PA activities after the end of the epidemic. Second, colleges offer physical education classes for four academic years of college students to promote PA and PF.

The expansion and evolution of urban areas are the most perceptible manifestations of the transformation of the urban spatial form. This study uses remote sensing images of Nanjing from 2001, 2006, 2011, 2016, and 2021, along with socio-economic data to analyse the spatio-temporal characteristics of the city’s urban expansion. Furthermore, we utilize a binary logistic regression to quantitatively analyse the driving forces in each stage. We find that from 2001 to 2021, Nanjing’s urban area expanded approximately 3.97 times. Notably, the city started moving from a stage of medium-speed development to rapid development in 2006, and then slowed down and returned to medium-speed development in 2011. The urban land mainly expanded in the north, northeast, southeast, and southwest directions in a lopsided cross-shape roughly along the northwest-southeast direction; meanwhile, the city’s centre of gravity continuously moved towards the southeast. Among the driving factors, neighbourhood (distance from planned commercial centres, railways, and highways), topography, and geolocation (distance from the Yangtze River, and elevation) had a greater, albeit inhibitory effect on urban expansion. However, the effects of different socio-economic factors (GDP per capita, resident population, secondary and tertiary industry, etc.) varied across different time periods.

Secondary organizing pneumonia (SOP) is a nonspecific inflammatory response towards acute lung injuries caused by various diseases. However, organizing pneumonia (OP) secondary to occupational acute nitrogen oxide poisoning has been reported rarely. We report a 49-year-old man who suffered from nitrogen oxide poisoning after inhaling mixed gas at work. After pathological examination, he was diagnosed with OP. In the absence of other underlying factors causing OP, he was diagnosed with SOP owing to acute nitrogen oxide poisoning. After systematic treatment, the patient recovered and was discharged in better health. In patients with lung injury caused by acute nitrogen oxide poisoning, physicians should be alert to the risk of patients subsequently developing SOP, and timely diagnosis and treatment are essential for complete recovery.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with no curative treatments. Plexin D1 (PLXND1) is a cellular receptor whose functions have been explored in several human cancers; however, the critical roles of PLXND1 in HCC have rarely been probed. Therefore, the present study attempted to elucidate the expression pattern, prognostic significance, and potential roles of PLXND1 in HCC. We found that PLXND1 expression in HCC tissues was significantly higher compared with normal liver tissue from Gene Expression Profiling Interactive Analysis (GEPIA) and Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB) databases. This result was further validated by immunohistochemistry staining (IHC) using tissue microarrays, which contained 216 HCC cases collected from our hospital. Additionally, PLXND1 expression showed a significant correlation with several clinical characteristics, including tumor grade and tumor hemorrhage (TH). Moreover, TISIDB and GEPIA databases were used to investigate the roles of PLXND1 in tumor-immune system interactions in HCC. As an immunoinhibitor, transforming growth factor-beta (TGF-β1) displayed the greatest correlations with PLXND1 in HCC. Finally, Kaplan-Meier curves and Cox analysis were conducted to further examine the potential clinical value of PLXND1 in HCC. We described a subclassification of HCC based on PLXND1 and TGF-β1 expression, which could be used to predict clinical outcomes and patient prognosis. Taken together, the results of this study indicate that PLXND1 might be a promising prognostic biomarker and potential therapeutic target in HCC.

Patients who commit suicide often deliberately hide their medical history. Given that taking pesticides is one of the most common methods of suicide, other forms of poisoning may be neglected in clinical practice. We report here a case of mixed-pesticide poisoning. The patient was poisoned by oral administration of a coumarin rodenticide in combination with an intramuscular injection of organophosphorus (OP) pesticide. The patient was treated with vitamin K1, cholinesterase reactivators, atropine, ventilator-assisted ventilation, and bedside debridement. Her condition gradually stabilized and she eventually recovered and was discharged. Assessment of the causes of delayed diagnosis and treatment suggests that we need to improve early detection and treatment of acute poisoning. It is especially important to ask about the patient’s medical history, conduct a careful physical examination, and track the clinical symptoms and differential diagnosis of common poisoning. In addition to the three common routes of poisoning—oral, inhalation, and cutaneous mucosal contact—intramuscular injection of OP can also lead to severe poisoning, which manifests as respiratory failure.

Abstract Backgroud Accumulating evidences indicate that circular RNAs (circRNAs), a class of non-coding RNAs, play important roles in tumorigenesis. However, the function of circRNAs in hepatocellular cancer (HCC) is largely unknown. Methods We performed circRNA microarrays to identify circRNAs that are aberrantly expressed in HCC tissues. Expression levels of a significantly upregulated circRNA, circFBLIM1, was detected by quantitative real-time PCR (qRT-PCR) in HCC cell lines and tissues. Then, we examined the functions of circFBLIM1 in HCC by cell proliferation, apoptosis, invasion and mouse xenograft assay. In addition, luciferase assay and RNA immunoprecipitation (RIP) assay were used to explore the miRNA sponge function of circFBLIM1 in HCC. Results Microarray analysis and qRT-PCR verified a circRNA termed circFBLIM1 that was upregulated in HCC tissues and cell lines. Knockdown of circFBLIM1 inhibited proliferation, invasion and promoted apoptosis in HCC. Via luciferase reporter assays, circFBLIM1 and FBLIM1 were observed to directly bind to miR-346. Subsequent experiments showed that circFBLIM1 and FBLIM1 regulated the expression of each other by sponging miR-346. Conclusions Taken together, we conclude that circFBLIM1 may function as a competing endogenous RNA (ceRNA) to regulate FBLIM1 expression through sponging miR-346 to exert regulatory functions in HCC. circFBLIM1 may be a diagnostic biomarker and potential target for HCC therapy.

Background Many recent studies have demonstrated the predominant role chronic inflammation plays in cancer cell propagation, angiogenesis and immunosuppression. Cancer-related inflammation (CRI) has been shown to correlate with poor cancer prognosis. Our study aimed to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with hepatocellular carcinoma (HCC) who have undergone liver resection. Methods Between 2012 and 2015, 239 patients with HCC who had undergone liver resection at XiangYa Hospital Central South University were included in this study. The values of simple inflammatory markers, including the NLR and PLR, used in predicting the long-term outcomes of these patients were evaluated using Kaplan–Meier curves and Cox regression models. Results The cutoff values of the NLR and PLR were 2.92 and 128.1, respectively. In multivariate Cox regression analysis, high NLR (≥2.92) and high PLR (≥128.1) were independent risk factors predicting poorer outcomes in patients with HCC. However, high NLR and high PLR were prognostic factors in tumor size and tumor number. Conclusions In this study, we identified that high NLR (≥2.92) and high PLR (≥128.1) are useful prognostic factors in predicting outcomes in patients with HCC whom underwent liver resection.

Objective: To explore the relation between procrastination and physical activity in college students and test whether grit mediated, age and gender moderated the process. Participants: 610 college students (aged 20.07 ± 1.53; 45.2% males) in Shanghai. Methods: Procrastination, grit and physical activity were tested respectively by International Procrastination Scale, Grit-S scale and International Physical Activity Questionnaire. Results: Correlation analysis showed that procrastination, grit and physical activity were related in pairs. Procrastination was negatively correlated with physical activity. Grit mediated between procrastination and physical activity. Females showed stronger moderation effect from grit to physical activity than males, while the effect between procrastination and grit was more significant for the younger. Conclusion: The moderated mediating model provided a new strategy of improving personality traits which contributed to lack of physical activity. More psychologically relevant measures should be taken in reducing procrastination to improve physical activity via improving grit.

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. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma is one of the most common tumors in humans. By exploring the role of necroptosis in lung adenocarcinoma, we aimed to gather information which can be used to build a necroptosis-related-gene-based diagnostic model that can play an auxiliary role in lung adenocarcinoma diagnosis and treatment. Necroptosis-related genes were selected from the Kyoto Encyclopedia of genes and genomes database. Differentially expressed genes in the tumor group and normal group were identified from The Cancer Genome Atlas/Genomic Data Commons database then analyzed by gene ontology, Kyoto Encyclopedia of genes and genomes and gene set enrichment analysis. Cox and Lasso regression analyses were used to screen out prognosis-related necroptosis-related genes from the differentially expressed genes and establish a necroptosis risk-scoring signature. The receiver operating characteristic curves were plotted and patients were divided into high-risk and low-risk groups according to the necroptosis risk-scoring signature. Kaplan-Meier survival curves were drawn and area under the curve, and decision curve analyses were calculated to evaluate the performance of the model. Then, internal and external dataset validations were performed. A total of 159 necroptosis-related genes were retrieved from the Kyoto Encyclopedia of genes and genomes database, 39 of which were differentially expressed in tumor tissues. Four necroptosis-related genes (interleukin-33, cytochrome B-245 beta chain, H2A.X variant histone and Readthrough (RNF103-CHMP3)) independently correlated with lung adenocarcinoma prognosis were screened by Lasso or Cox regression based on which prognostic model was established. The independent prognostic value of this model was verified by multivariate Cox regression analysis. In this model, the low-risk group showed significantly longer survival time than the high-risk group (p<0.01) and the model showed good predictive performance in both the internal and external validation sets. In this study, we explored the potential link between necroptosis and lung adenocarcinoma, established a necroptosis gene-based prognostic model and validated the independent prognostic value of the model. [ABSTRACT FROM AUTHOR]

Apoptosis and necroptosis occur in renal tubular epithelial cell (RTEC) death in acute kidney injury (AKI), and may be regulated by several methods. The present study identified a protective effect of necrostatin-1 (Nec-1) on RTECs via a flow-control-like effect. The results established a hypoxic-ischemic injury model of rat NRK-52E RTECs using tumour necrosis factor-α followed by ATP depletion with antimycin A and the pan-caspase pathway blocker, benzyloxycarbonyl-Val-Ala-Asp-fluoro-methylketone. Following pre-treatment of cells with Nec-1, cell organelle inflation, fragmentation inhibition and improved cell viability were observed with a parallel reduced expression of microtubule-associated protein 1A/1B-light chain 3-II. Nec-1 was involved in flow control in the process of cell injury and death. In conclusion, the present study indicated that Nec-1 provides a protective effect and serves an important role in the prevention of AKI in an NRK-52E cell model. Further studies will be required to fully investigate the role of Nec-1 in the development of AKI in vivo. [ABSTRACT FROM AUTHOR]

Assessment of hepatic functional reserve is important to enable the selection of appropriate treatment methods and safe hepatic resection in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). In the present study, an evaluation was made of the clinical value of combining the Child-Pugh score (CPS) with the standardized future liver remnant (sFLR) measurement to predict postoperative liver dysfunction (PLD). A total of 61 HBV-related HCC patients undergoing liver volumetry prior to hepatectomy were enrolled in the study. The sFLR was calculated as the ratio of FLR volume to standardized liver volume. PLD was defined as a prothrombin time of >18 sec or a peak serum bilirubin level of >51.3 μmol/l for 7 days after surgery. Univariate analysis and multivariate logistic regression analysis were performed to identify risk factors associated with PLD. The correlation between PLD and the combination of sFLR and CPS was analyzed. In total, 18 out of 61 patients developed PLD (29.5%), with a significantly higher PLD incidence for a CPS of 6 than a CPS of 5 (P<0.05). Multivariate logistic regression analysis revealed that a prothrombin time of <13.3 sec and an sFLR of <0.55 were independent risk factors for PLD. Receiver operating characteristic (ROC) curve analysis revealed that the cut-off values of sFLR and sFLR/CPS for predicting PLD were 54.5% and 0.0916, respectively, with areas under the ROC curve of 0.820 and 0.860, respectively. The combination of CPS and sFLR appears to yield improved prediction of the occurrence of PLD compared with either CPS or sFLR alone. [ABSTRACT FROM AUTHOR]

Background The correlation between proteinuria and contrast-induced acute kidney injury (CI-AKI) in patients with cerebrovascular disease is still unknown. Objective To determine whether proteinuria is a risk factor for CI-AKI and death in patients with stroke undergoing cerebral angiography. Methods Data from 2015 patients with stroke undergoing cerebral angiography between January 2009 and December 2013 were retrospectively collected. Clinical parameters were obtained from the hospital's computerized database. All variables were analyzed by univariate analysis and multivariate logistic regression analysis. Results CI-AKI was seen in 85 patients (4.2%). After adjustment for potential confounding risk factors, patients with proteinuria had a fivefold higher risk of CI- AKI than patients without proteinuria (OR=5.74; 95% CI 2.23 to 14.83; p<0.001). Other independent risk factors for CI-AKI were estimated glomerular filtration rate <60 mL/min/1.73 m², anemia, and a high National Institute of Health Stroke Scale score. Proteinuria did not increase in-hospital mortality (OR=1.25; 95% CI 0.49 to 3.17; p=0.639) but did increase 1-year mortality (HR=2.30, 95% CI 1.55 to 3.41, p<0.001). Conclusions Proteinuria is an independent risk factor for CI-AKI and 1-year mortality in patients with stroke undergoing cerebral angiography. More attention should be paid to the development of CI-AKI in patients with stroke with proteinuria. [ABSTRACT FROM AUTHOR]

Anaplastic thyroid carcinoma (ATC) is an aggressive malignant disease in older adults with a high mortality rate. The present study aimed to examine several key genes and pathways, which are associated with ATC. The GSE33630 gene expression profile was downloaded from the Gene Expression Omnibus database, which included 11 ATC and 45 normal thyroid samples. The differentially expressed genes (DEGs) in ATC were identified using the Limma package in R. The Gene Ontology functions and Kyoto Encyclopedia of Genes and Genomes pathways of the selected DEGs were enriched using the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction (PPI) network of the DEGs was constructed to select significant modules. Furthermore, a latent pathway interactive network was constructed to select the significant pathways associated with ATC. A total of 665 DEGs in the ATC samples were screened, and four significant modules were selected from the PPI network. The DEGs in the four modules were enriched in several functions and pathways. In addition, 29 significant pathways associated with ATC were selected, and he Toll-like receptor (TLR) signaling pathway, extracellular matrix (ECM)-receptor interaction and cytokine-cytokine interaction pathway were identified as important pathways. FBJ murine osteosarcoma viral oncogene homolog (FOS), chemokine C-X-C motif ligand 10 (CXCL10), collagen type V a1 (COL5A1) and chemokine (C-C motif) ligand 28 (CCL28) were the key DEGs involved in these significant pathways. The data obtained in the present study revealed that the TLR signaling pathway, ECM-receptor interaction and cytokine-cytokine receptor interaction pathway, and the FOS, CXCL10, COL5A1, COL11A1 and CCL28 genes have different roles in the progression of ATC, and these may be used as therapeutic targets for ATC. [ABSTRACT FROM AUTHOR]

Purpose: E3 ubiquitin ligase ZNRF3 is linked to the pathogenesis of diseases and tumorigenesis. The present study aims to explore the expression of ZNRF3 and its association with prognostic survival of human colorectal carcinoma. Methods: A follow-up survey of 168 patients with colorectal carcinoma was performed, and specimens of colorectal tissues were collected for immunohistochemistry and Western blotting analyses. Furthermore, overexpression of ZNRF3 using transient transfection with the recombinant pEGFP-ZNRF3 plasmid and detection of apoptosis and proliferation were performed in HCT-116 cells. Results: The results showed a diverse feature of ZNRF3 staining, such as strong, moderate, weak, or negative, in colorectal carcinoma tissues. Interestingly, univariate Kaplan-Meier analysis showed that cases with strong or moderate expression of ZNRF3 showed an optimistic disease-free survival and overall survival compared with negative expression of ZNRF3, and multivariate Cox model demonstrated ZNRF3 as an independent prediction index for overall survival and disease-free survival. In vitro, the overexpression of ZNRF3 was related to the negative regulation of Wnt/ß-catenin pathway and referred to an induction of apoptosis and suppression of proliferation in ZNRF3-transfected HCT-116 cells. Conclusion: Our results suggest that the higher expression of ZNRF3 acts as a novel marker of indicating the optimistic prognosis of colorectal carcinoma by suppressing cancer cell growth and facilitating apoptosis. [ABSTRACT FROM AUTHOR]

Background: Neuron navigator 2 (NAV2) encodes a member of the neuron navigator gene family, which plays a role in tumorigenesis and cell migration. However, the prognostic value of NAV2 expression in colorectal cancer (CRC) patients and the potential pathway through which NAV2 promotes migration and invasion in CRC cell lines is poorly understood. Methods: The expression level of NAV2 was detected in CRC tissues from two different CRC cohorts by immunohistochemistry, qRT-PCR and Western blotting; the correlation between NAV2 expression and clinicopathological characters was analyzed, and the prognostic value of NAV2 expression was analyzed using a Cox regression model. CRC cell lines with NAV2 knocked out were used to validate the function and potential pathway used by NAV2 to promote CRC cell migration and invasion. Results: The results showed that NAV2 was overexpressed in CRC tissues, and it was closely correlated with depth of invasion, and lymph and distant metastasis. Multivariate analysis indicated that high NAV2 expression was a poor prognostic indicator of recurrence-free survival and overall survival in CRC patients. Furthermore, Cox regression analysis revealed that high NAV2 expression integrated with high tumor budding grade was a powerful independent predictive factor of CRC clinical outcome. In vitro and in vivo assays demonstrated that knockdown of NAV2 led to reduced migration and invasion of cancer cells, and the process involved the regulation of F-actin polymerization through the SSH1L/cofilin-1 pathway. Conclusion: Based on these findings, NAV2 could serve as both a prognostic biomarker and a potential therapeutic target for patients with NAV2-positive CRC. [ABSTRACT FROM AUTHOR]