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Abstract Objective To investigate the prognostic significance of CXCL8 in cervical cancer and its effect on immune response based on bioinformatics method. Methods This study employs the HPA database to investigate CXCL8 expression in normal human tissues.The TIMER2.0 database is utilized to analyze CXCL8 expression across various types of cancer.Utilizing the TCGA database, we analyze the correlation between CXCL8 and the overall survival (OS) and progression-free interval (PFI) of patients with various tumors using R 4.3.2.Additionally, its association with immune checkpoint-related genes across various types of cancer is examined.We further analyze the association between CXCL8 expression and the expression of LAG3, CTLA4, PDCD1, and CD274 in cervical cancer.The TIMER database is used to study the association between CXCL8 and the extent of Tumor-Infiltrating Immune Cells (TIICs) infiltration.Enrichment analysis of genes related to CXCL8 is conducted using the LinkedOmics database. Result CXCL8 is found in a wide range of normal human tissues.In the majority of tumor tissues, CXCL8 expression is elevated compared to their normal counterparts.There is a significant correlation between CXCL8 expression and the overall survival (OS) and progression-free interval (PFI) of patients with various tumors.CXCL8 expression is associated with the expression of diverse immune checkpoint-related genes and the extent of Tumor-Infiltrating Immune Cells (TIICs) infiltration.Genes related to CXCL8 participate in diverse immune-related processes in cervical cancer. Conclusion CXCL8 plays a role in modulating immune infiltration, thereby influencing the prognosis of patients with various tumors, particularly those with cervical cancer.CXCL8 could potentially act as a biomarker for forecasting the prognosis and immune response of patients with tumors.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infection with a high case fatality rate. Significant gaps remain in studies analyzing the clinical characteristics of fatal cases. Methods From January 2017 to June 2023, 427 SFTS cases were included in this study. A total of 67 variables about their demographic, clinical, and laboratory data were collected. Univariate logistic regression and the least absolute shrinkage and selection operator (LASSO) method was used to screen predictors from the cohort. Multivariate logistic regression was used to identify independent predictors and nomograms were developed. Calibration, decision curves and area under the curve (AUC) were used to assess model performance. Results The multivariate logistic regression analysis screened out the four most significant factors, including age > 70 years (p = 0.001, OR = 2.516, 95% CI 1.452–4.360), elevated serum PT (p 8.0 μmol/L) (p

Aiming to explore the meaning and value of the space of a sports club for university students in South Korea, this study employs the idea of spatial culture by Henri Lefebvre. The foundation of the cultural experience of a sports club is the cultural experience of a specific space; therefore, this paper takes the concern of spatial culture as the theoretical starting point. The research method is participant observation, and the researchers explored a sports club culture in South Korea for 4 months. The topics discussed in this study, such as, the boundaryless atmosphere within the sports club which provides the possibility for students to seek empathy; the sports club provides an obvious boundary with daily life which allows students to build another identity for resisting dissatisfaction with life; and last, it also provides the possibility of learning for students in a changing and diverse campus environment.

Abstract Background To retrospectively analyze the risk factors of liver metastases in patients with gastric cancer in a single center, and to establish a Nomogram prediction model to predict the occurrence of liver metastases. Methods A total of 96 patients with gastric cancer who were also diagnosed with liver metastasis (GCLM) and treated in our center from January 1, 2010 to December 31, 2020 were included. The clinical data of 1095 patients with gastric cancer who were diagnosed without liver metastases (GC) in our hospital from January 1, 2014 to December 31, 2017 were retrospectively compared by univariate and multivariate logistic regression. 309 patients diagnosed with gastric cancer in another medical center from January 1, 2014 to December 31, 2018 were introduced as external validation cohorts. Results Based on the training cohort, multivariate analysis revealed that tumor site (OR = 0.55, P = 0.046), N stage (OR = 4.95, P = 0.004), gender (OR = 0.04, P = 0.001), OPNI (OR = 0.95, P = 0.041), CEA (OR = 1.01, P = 0.018), CA724 (OR = 1.01, P = 0.006), CA242 (OR = 1.01, P = 0.006), WBC (OR = 1.13, P = 0.024), Hb (OR = 0.98, P

Abstract Background To explore the role of GAB2 in pan-cancer based on bioinformatics analysis. Methods Based on TCGA and GTEx databases, we used TIMER2.0 online analysis tool and R language to analyze the expression of GAB2 in pan-cancer. We used Kaplan–Meier Plotter to analyze the relationship between GAB2 and OS and RFS in pan-cancer. We utilized the CPTAC database to examine the expression of phosphorylated GAB2 in pan-cancer. We investigated the effects of mutation features on the occurrence and development of human cancers by cBioPortal and COSMIC. Using the database, we conducted an analysis of molecular compounds that have the potential to interact with GAB2 through molecular docking. Moreover, we use the TIMER to explore the relationship between GAB2 and immune cell infiltration, and draw relevant heatmaps by R language. Results GAB2 was abnormally expressed in various tumors and was associated with prognosis. There were differences in the expression of GAB2 phosphorylation in tumor tissues and corresponding normal tissues among different types of tumors. GAB2 interacts with Docetaxel and was associated with immune cell infiltration in various tumors. Conclusion GAB2 participates in regulating immune infiltration and affects the prognosis of patients. GAB2 may serve as a potential tumor marker.

Abstract This study aims to explore the risk factors associated with frozen shoulder (FS) and develop a predictive model for diagnosing FS, in order to facilitate early detection of the condition. A total of 103 patients diagnosed with FS and admitted to the Department of Joint Surgery at Suining Central Hospital between October 2021 and October 2023 were consecutively included in the study. Additionally, 309 individuals without shoulder joint diseases, matched for age and gender, who visited the department during the same time, were included as the control group.The complete recording of clinical data for all patients was followed by the utilization of statistical tests such as the Mann–Whitney U test, sample t test, and chi-square test to compare different groups. Additionally, multivariate binary logistic regression analysis was employed to identify risk factors associated with the occurrence of FS in patients, leading to the establishment of a prediction model and derivation of a simplified equation. The diagnostic effectiveness of individual indicators and prediction models was assessed through the use of receiver operating characteristic (ROC) curve analysis. In the sample of 103 individuals, 35 were identified as male and 68 as female, with an average age range of 40–70 years (mean age: 54.20 ± 6.82 years). The analysis conducted between different groups revealed that individuals with a low body mass index (BMI), in conjunction with other factors such as diabetes, cervical spondylosis, atherosclerosis, and hyperlipidemia, were more susceptible to developing FS. Logistic regression analysis further indicated that low BMI, diabetes, cervical spondylosis, and hyperlipidemia were significant risk factors for the occurrence of FS. These variables were subsequently incorporated into a predictive model, resulting in the creation of a simplified equation.The ROC curve demonstrated that the combined indicators in the predictive model exhibited superior diagnostic efficacy compared to single indicators, as evidenced by an area under the curve of 0.787, sensitivity of 62.1%, and specificity of 82.2%. Low BMI, diabetes, cervical spondylosis, and hyperlipidemia are significant risk factors associated with the occurrence of FS. Moreover, the utilization of a prediction model has demonstrated superior capability in forecasting the likelihood of FS compared to relying solely on individual indicators. This finding holds potential in offering valuable insights for the early diagnosis of FS.

Abstract Introduction Intracerebral hemorrhage (ICH) is a severe manifestation of stroke, demonstrating notably elevated global mortality and morbidity. Thus far, effective therapeutic strategies for ICH have proven elusive. Currently, minimally invasive techniques are widely employed for ICH management, particularly using endoscopic hematoma evacuation in cases of deep ICH. Exploration of strategies to achieve meticulous surgery and diminish iatrogenic harm, especially to the corticospinal tract, with the objective of enhancing the neurological prognosis of patients, needs further efforts. Methods We comprehensively collected detailed demographic, clinical, radiographic, surgical, and postoperative treatment and recovery data for patients who underwent endoscopic hematoma removal. This thorough inclusion of data intends to offer a comprehensive overview of our technical experience in this study. Results One hundred fifty-four eligible patients with deep supratentorial intracerebral hemorrhage who underwent endoscopic hematoma removal were included in this study. The mean hematoma volume was 42 ml, with 74 instances of left-sided hematoma and 80 cases of right-sided hematoma. The median Glasgow Coma Scale (GCS) score at admission was 10 (range from 4 to 15), and the median time from symptom onset to surgery was 18 (range 2 to 96) h. The mean hematoma clearance rate was 89%. The rebleeding and mortality rates within 1 month after surgery were 3.2% and 7.8%, respectively. At the 6-month mark, the proportion of patients with modified Rankin Scale (mRS) scores of 0–3 was 58.4%. Conclusion Both the reduction of surgery-related injury and the protection of the residual corticospinal tract through endoscopic hematoma removal may potentially enhance neurological functional outcomes in patients with deep ICH, warranting validation in a forthcoming multicenter clinical study.

Abstract Background A few previous cross-sectional studies investigated correlated factors of suicidal ideation or suicide attempts among suicide prevention hotline callers; however, scarcely any evidence was from a longitudinal study. In addition, it is still unclear whether improvements in some suicide risk factors could reduce the occurrence of subsequent suicidal acts. This longitudinal study focusing on the risk factors for subsequent suicidal acts among adolescent and young adult callers with high suicide risk aims to fill this gap. Methods This study recruited 12–25-year-old high-risk callers to a China nationwide suicide prevention hotline. Potential risk factors, including hopefulness, psychological distress, depression, history of suicide attempts, alcohol or substance misuse, and acute life events, were examined during the index calls, and improvements in hopefulness, psychological distress, and suicide intent were assessed before ending the index calls. The recruited callers were followed up 12 months after their index calls. The primary outcome was the occurrence of suicidal acts (suicide attempts or suicide death) during follow-up. Kaplan–Meier survival curves, log-rank tests, and Cox proportional hazards model were used. Results During the follow-up period, 271 of 1656 high-risk adolescent and young adult callers attempted suicide, and seven callers died by suicide. After adjusting for demographic variables, low hopefulness (Hazard Ratio [HR] = 2.03, 95% Confidence Interval [CI]=[1.47, 2.80]) at the beginning of the index call was associated with a higher risk for subsequent suicidal acts, whereas improvements in psychological distress (HR = 0.61, 95%CI [0.41, 0.89]) and suicidal intent (HR = 0.56, 95%CI [0.38, 0.84]) during the index call reduced the risk of subsequent suicidal acts. In addition, alcohol or substance misuse (Model 2, HR = 1.65, 95%CI [1.11, 2.46]) and suicide attempt history(Model 1: one episode, HR = 1.96, 95%CI=[1.05, 3.66]; two or more episodes, HR = 2.81, 95%CI [1.59, 4.96]. Model 2: one episode, HR = 2.26, 95%CI [1.06, 4.82]; two or more episodes: HR = 3.28, 95%CI [1.63, 6.60]) were risk factors for subsequent suicidal acts. Conclusions While suicide prevention hotline operators deliver brief psychological interventions to high-risk adolescent and young adult callers, priority should be given to callers with low hopefulness and to the alleviation of callers’ high psychological distress and suicide intent.

Abstract Although it is well documented that mountains tend to exhibit high biodiversity, how geological processes affect the assemblage of montane floras is a matter of ongoing research. Here, we explore landform-specific differences among montane floras based on a dataset comprising 17,576 angiosperm species representing 140 Chinese mountain floras, which we define as the collection of all angiosperm species growing on a specific mountain. Our results show that igneous bedrock (granitic and karst-granitic landforms) is correlated with higher species richness and phylogenetic overdispersion, while the opposite is true for sedimentary bedrock (karst, Danxia, and desert landforms), which is correlated with phylogenetic clustering. Furthermore, we show that landform type was the primary determinant of the assembly of evolutionarily older species within floras, while climate was a greater determinant for younger species. Our study indicates that landform type not only affects montane species richness, but also contributes to the composition of montane floras. To explain the assembly and differentiation of mountain floras, we propose the ‘floristic geo-lithology hypothesis’, which highlights the role of bedrock and landform processes in montane floristic assembly and provides insights for future research on speciation, migration, and biodiversity in montane regions.

Abstract Background Clozapine is an off-label drug used in most countries to prevent suicide in individuals with schizophrenia. However, few studies have reported real-world prescription practices. This study aimed to explore the association between a history of suicidal behavior and clozapine prescribing during eight weeks of hospitalization for individuals with early-stage schizophrenia. Methods This observational cohort study used routine health data collected from a mental health hospital in Beijing, China. The study included 1057 inpatients who had schizophrenia onset within 3 years. History of suicidal behavior was coded from reviewing medical notes according to the Columbia Suicide Severity Rating Scale. Information on antipsychotic use during hospitalization was extracted from the prescription records. Time to clozapine use was analyzed using Cox regression models adjusted for sociodemographic and clinical covariates. Results The prevalence rates of self-harm, suicidal behavior, and suicide attempt were 12.3%, 7.5%, and 5.4%, respectively. A history of self-harm history was positively associated with clozapine uses upon admission (4.1% vs. 0.8%, exact p = 0.009). Among those who had not used clozapine and had no clozapine contraindication, A history of suicidal behavior increased the possibility of switch to clozapine within 56 days after admission (Hazard Ratio[95% CI], 6.09[2.08–17.83]) or during hospitalization (4.18[1.62–10.78]). Conclusion The use of clozapine for early-stage schizophrenia was more frequent among those with suicidal behavior than among those without suicidal behavior in China, although the drug instructions do not label its use for suicide risk.

Abstract Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated the spatiotemporal heterogeneity of CC molecular expression during malignant transformation. It was found that although both tight junctions (TJs) and gap junctions (GJs) were involved in maintaining the tumor microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), the expression of TJ molecules consistently decreased during normal-cancer transformation and is a potential oncogenic factor. For fibroblasts (mesenchymal component), the expression of GJs consistently increased during normal-cancer transformation and is a potential oncogenic factor. In addition, the molecular profiles of TJs and GJs were used to stratify colorectal cancer (CRC) patients, where subtypes characterized by high GJ levels and low TJ levels exhibited enhanced mesenchymal signals. Importantly, we propose that leiomodin 1 (LMOD1) is biphasic, with features of both TJs and GJs. LMOD1 not only promotes the activation of cancer-associated fibroblasts (CAFs) but also inhibits the Epithelial–mesenchymal transition (EMT) program in cancer cells. In conclusion, these findings demonstrate the molecular heterogeneity of CC and provide new insights into further understanding of TME heterogeneity. Graphical Abstract

CRISPR-Cas9 genome editing has promising therapeutic potential for genetic diseases and cancers, but safety could be a concern. Here we use whole genomic analysis by 10x linked-read sequencing and optical genome mapping to interrogate the genome integrity after editing and in comparison to four parental cell lines. In addition to the previously reported large structural variants at on-target sites, we identify heretofore unexpected large chromosomal deletions (91.2 and 136 Kb) at atypical non-homologous off-target sites without sequence similarity to the sgRNA in two edited lines. The observed large structural variants induced by CRISPR-Cas9 editing in dividing cells may result in pathogenic consequences and thus limit the usefulness of the CRISPR-Cas9 editing system for disease modeling and gene therapy. In this work, our whole genomic analysis may provide a valuable strategy to ensure genome integrity after genomic editing to minimize the risk of unintended effects in research and clinical applications.

BackgroundPralsetinib, a selective oral inhibitor of rearranged during transfection (RET) fusion proteins and oncogenic RET mutants, has shown significant efficacy in treating RET fusion-positive non-small cell lung cancer and thyroid cancer. However, since pralsetinib was approved in the United States in September 2020, there have been limited reports of post-marketing adverse events (AEs). In this study, we aimed to analyze the AE signals with pralsetinib on the basis of the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to provide instructions in clinical practice.MethodsAll AE reports were obtained from the FAERS database from the first quarter (Q3) of 2020 to the second quarter (Q2) of 2024. Various signal quantification techniques were used for analysis, including reporting odds ratios, proportional reporting ratios, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker (MGPS)-based empirical Bayesian geometric mean.ResultsOut of 8,341,673 case reports in the FAERS database, 1,064 reports of pralsetinib as the “primary suspected (PS)” AEs were recorded, covering 26 system organ classes and 256 preferred terms. Of the reports, 62.5% were from consumers rather than healthcare professionals. The most common systems were general disorders and administration site conditions (n = 704), investigations (n = 516), and gastrointestinal disorders (n = 405). A total of 95 significant disproportionality preferred terms (PTs) conformed to the four algorithms simultaneously. AEs that ranked the top three at the PT level were hypertension (n = 80), asthenia (n = 79), and anemia (n = 65). Of the 95 PTs with significant disproportionation, unexpected significant AEs such as increased blood calcitonin, increased myocardial necrosis marker, and bacterial cystitis were observed, which were not mentioned in the drug’s instructions. The median onset time of pralsetinib-associated AEs was 41 days [interquartile range (IQR) 14–86 days]. The majority of the AEs occurred in 30 days (42.86%).ConclusionOur pharmacovigilance analysis of real-world data from the FEARS database revealed the safety signals and potential risks of pralsetinib usage. These results can provide valuable evidence for further clinical application of pralsetinib and are important in enhancing clinical medication safety.

The radial load distribution integral given by Harris integral method always plays a significant role in calculating the radial load distribution of radial bearings. The error of Harris integral method for calculating the radial load distribution is found caused by the inaccurate values of the radial load distribution integral given by Harris. The radial load distribution integral is corrected in three loading stages using a discrete method. The corrected radial load distribution integral is capable of calculating the load distribution of a bearing with a small load zone caused by a light external load or a great radial clearance. The corrected radial load distribution integral shows different phases varying with the number of rolling elements participating in the radial load transfer. Some specific numerical examples show the higher accuracy and superiority of the corrected radial load distribution integral.

Background Pulmonary arterial hypertension (PAH) is a complex, fatal disease where disease severity has been associated with the single nucleotide polymorphism (SNP) rs2856830, located near the human leukocyte antigen DPA1 (HLA-DPA1) gene. We aimed to define the genetic architecture of functional variants associated with PAH disease severity by identifying allele-specific binding transcription factors and downstream targets that control endothelial pathophenotypes and PAH. Methods and Results Electrophoretic mobility shift assays of oligonucleotides containing SNP rs2856830 and 8 SNPs in linkage disequilibrium revealed functional SNPs via allele-imbalanced binding to human pulmonary arterial endothelial cell nuclear proteins. DNA pulldown proteomics identified SNP-binding proteins. SNP genotyping and clinical correlation analysis were performed in 84 patients with PAH at University of Pittsburgh Medical Center and in 679 patients with PAH in the All of Us database. SNP rs9277336 was identified as a functional SNP in linkage disequilibrium (r2>0.8) defined by rs2856830, and the minor allele was associated with decreased hospitalizations and improved cardiac output in patients with PAH, an index of disease severity. SNP pulldown proteomics showed allele-specific binding of nuclear ACTN4 (alpha actinin 4) protein to rs9277336 minor allele. Both ACTN4 and HLA-DPA1 were downregulated in pulmonary endothelium in human patients and rodent models of PAH. Via transcriptomic and phenotypic analyses, knockdown of HLA-DPA1 phenocopied knockdown of ACTN4, both similarly controlling cell structure pathways, immune pathways, and endothelial dysfunction. Conclusions We defined the pathogenic activity of functional SNP rs9277336, entailing the allele-specific binding of ACTN4 and controlling expression of the neighboring HLA-DPA1 gene. Through inflammatory or genetic means, downregulation of this ACTN4-HLA-DPA1 regulatory axis promotes endothelial pathophenotypes, providing a mechanistic explanation for the association between this SNP and PAH outcomes.

Abstract Quark-gluon plasma’s (QGP) properties at non-hydrodynamic and non-perturbative regimes remain largely unexplored. Here, we examine the response functions describing how a QGP-like plasma responds to initial energy-momentum disturbance in both static and Bjorken-expanding plasma at non-hydrodynamic gradient using the Boltzmann equation in the relaxation-time approximation (RTA). We show that the resulting response functions are remarkably similar in both static and expanding backgrounds at non-hydrodynamic gradients. While non-hydrodynamic response can not be described by the conventional first-order and second-order theories, its behavior is reasonably captured by the extended version of hydrodynamics proposed by us [1]. The potential sensitivity of the Euclidean correlator to non-hydrodynamic response is also illustrated.

Abstract The illegal water injection into meat not only breaks the market equity, but also deteriorates the meat quality and produces harmful substances. In this work, we proposed a fiber Bragg grating (FBG) sensor that enabled fast, quantitative, and in-situ detection of the moisture content of water-injected meat. The FBG was written in the erbium-ytterbium (Er/Yb) co-doped fiber, which could perform the self-photothermal effect by injecting the near infrared laser into the fiber. As the heated fiber sensor probe was inserted into the meat sample, the temperature decreased due to the heat dissipation mediated by moisture. The intracore Bragg grating could monitor the temperature loss by recording the Bragg wavelength shift, which reflected the water content quantitatively. The results revealed that the sensor could complete the detection within 15 s. The sensor’s sensitivity to detect changes in the pork water content was theoretically calculated to be 0.090847%. The proposed sensor is expected to provide a novel approach for examination of the meat moisture.

Abstract Dynamic stress is one of the key indicators reflecting the fatigue characteristics of metro bogie frames. Considering the test costs, operation safety, and other factors, it is impossible to record all the dynamic stress data for the whole service period in the tracking test. Therefore, the overall stress spectrum is statistically deduced based on limited dynamic stress data samples, which can not only provide a basis for the fatigue reliability research of the bogie frame, but also save costs. In this paper, the typical fatigue control points in different areas of the frame with large equivalent stress are selected for research. The daily measured stress spectrum samples are obtained through the rainflow counting method, and the statistical stress spectrum is then compiled. Weibull distribution fitting of the stress spectrum is carried out to obtain the scale and shape parameter samples for different fatigue control parts. After sampling of the obtained parameter samples and conducting variance homogeneity tests as well as t-tests, the minimum sample size representing the overall distribution of the interval is obtained. Therefore, the shortest tracking test period reflecting the overall stress distribution of typical fatigue control parts can be obtained.

Abstract To quantitatively assess the diagnostic efficacy of multiple parameters derived from multi-b-value diffusion-weighted imaging (DWI) using turbo spin echo (TSE)–based acquisition techniques in patients with solitary pulmonary lesions (SPLs). A total of 105 patients with SPLs underwent lung DWI using single-shot TSE–based acquisition techniques and multiple b values. The apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM) parameters, and lesion-to-spinal cord signal intensity ratio (LSR), were analyzed to compare the benign and malignant groups using the Mann–Whitney U test and receiver operating characteristic analysis. The Dstar values observed in lung cancer were slightly lower than those observed in pulmonary benign lesions (28.164 ± 31.950 versus 32.917 ± 34.184; Z = -2.239, p = 0.025). The LSR values were significantly higher in lung cancer than in benign lesions (1.137 ± 0.581 versus 0.614 ± 0.442; Z = − 4.522, p

In order to understand the dynamic changes of non-volatile metabolites in Xinyang Maojian tea during processing, Xinyang Maojian tea samples from Xinyang tea population (Camellia sinensis cv. Quntizhong) taken during processing were systematically analyzed by non-targeted metabolomics. A total of 1 000 non-volatile metabolites were identified, and multivariate statistical analysis showed that non-volatile metabolites changed significantly during the processing stages after fixation. Meanwhile, a total of 53 differential compounds were screened out, including amino acids, catechins, flavonoid glycosides, lipids, purine nucleosides and organic acids that were identified as the key components contributing to the flavor and quality of Xinyang Maojian tea. In particular, the relative contents of some acylated flavonoid glycosides, lysophosphatidyls and purine nucleosides were significantly elevated during the processing stages after fixation. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway enrichment analysis showed that the differential compounds were significantly enriched in the pathways of purine metabolism, glycerophospholipid metabolism, phenylalanine metabolism, aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, and glycine, serine and threonine metabolism (P < 0.05). This study provides a basis for understanding the formation mechanism of the flavor and quality of Xinyang Maojian tea.

Abstract Objectives To evaluate the process and the comprehensiveness of advance care planning (ACP), we designed a national ACP-OSCE (Objective Structured Clinical Examination) program. Methods The program was designed as a 40-minute OSCE test. Participants were categorized as different ACP team members to illustrate realistic scenarios. Preceptors were asked to observe ACP professionals’ actions, responses, and communication skills during ACP with standardized patients (SP) through a one-way mirror. Participants’ communication skills, medical expertise, legal knowledge, empathetic response and problem-solving skills of ACP were also self-evaluated before and after OSCE. Thematic analysis was used for qualitative analysis. Results In Nov 2019, a total of 18 ACP teams with 38 ACP professionals completed the ACP-OSCE program, including 15 physicians, 15 nurses, 5 social workers, and 3 psychologists. After the ACP-OSCE program, the average score of communication skills, medical expertise, legal knowledge, empathetic response, ACP problem-solving all increased. Nurses felt improved in medical expertise, legal knowledge, and problem-solving skills, psychologists and social workers felt improved in legal knowledge, while physicians felt no improved in all domain, statistically. Thematic analysis showed professional skills, doctoral-patient communication, benefit and difficulties of ACP were the topics which participants care about. Meanwhile, most participants agreed that ACP-OSCE program is an appropriate educational tool. Conclusion This is the first national ACP-OSCE program in Asia. We believe that this ACP-OSCE program could be applied in other countries to improve the ACP process and quality.

Abstract NUP155 is reported to be correlated with tumor development. However, the role of NUP155 in tumor physiology and the tumor immune microenvironment (TIME) has not been previously examined. This study comprehensively investigated the expression, immunological function, and prognostic significance of NUP155 in different cancer types. Bioinformatics analysis revealed that NUP155 was upregulated in 26 types of cancer. Additionally, NUP155 upregulation was strongly correlated with advanced pathological or clinical stages and poor prognosis in several cancers. Furthermore, NUP155 was significantly and positively correlated with DNA methylation, tumor mutational burden, microsatellite instability, and stemness score in most cancers. Additionally, NUP155 was also found to be involved in TIME and closely associated with tumor infiltrating immune cells and immunoregulation-related genes. Functional enrichment analysis revealed a strong correlation between NUP155 and immunomodulatory pathways, especially antigen processing and presentation. The role of NUP155 in breast cancer has not been examined. This study, for the first time, demonstrated that NUP155 was upregulated in breast invasive carcinoma (BRCA) cells and revealed its oncogenic role in BRCA using molecular biology experiments. Thus, our study highlights the potential value of NUP155 as a biomarker in the assessment of prognostic prediction, tumor microenvironment and immunotherapeutic response in pan-cancer.

Abstract The purpose of this study was to explore whether dietary live microbe intake is associated with various cognitive domains using data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. And the specific relationship between low, medium and high dietary live microbe intake groups and cognitive ability of the elderly. Dietary live microbe intake was calculated from 24-h diet recall interviews. Cognitive function was assessed using the number symbol substitution test (DSST, which measures processing speed), the animal fluency test (AFT, which measures executive function), the Alzheimer's Registry sub-test (CERAD, which measures memory), and the Composite Z-score, which adds the Z-values of individual tests. Multiple linear regression models and restricted cubic bar graphs were used to investigate the relationship between live microbe intake and cognitive performance. A total of 2,450 participants aged 60 or older were included. Live microbe intake was positively correlated with cognitive ability on the whole. Specifically, when the intake of low, medium and high live microbe was > 2640 g, > 39 g and > 0 g respectively, the CERAD, DSST, AFT and compositive-Z score of the subjects increased with the increase of microbial intake (P

Abstract Background Chronic low back pain (LBP) related to flight is a prevalent health issue in military aviation, impacting pilots. The objective of this investigation was to ascertain if the application of core muscle training in conjunction with interferential current (IFC) therapy results in a reduction in pain severity and associated disability, consequently enhancing core muscle functionality in Chinese Air Force high-performance fighter pilots experiencing chronic LBP. Methods Fifty-three fighter pilots with chronic LBP were randomized into 3 groups: a core muscle exercise combined with IFC group (CG, n = 19), a core muscle exercise group (EG, n = 19), and an IFC group (IG, n = 15). The three groups underwent therapeutic intervention 5 times a week for 12 weeks. The primary outcomes were pain intensity, Oswestry Disability Index (ODI) score and SF-12 health-related quality of life (PCS and MCS) score. Secondary outcomes included evaluations of trunk muscle strength, endurance, and range of motion (ROM) during medial/lateral rotation to assess muscle functionality. Measurements were obtained both before and after the implementation of the intervention therapy. Results After 12 weeks of intervention therapy, all the health condition parameters significantly improved among the three groups. However, the CG had a significant improvement in pain intensity compared to the EG (MD = − 0.84 scores; 95% CI = − 1.54 to − 0.15; p = 0.013) and the IG (MD = − 1.22 scores; 95% CI = − 1.96 to − 0.48; p = 0.000). Additionally, the CG led to greater conservation of ODI and improved SF-12 PCS scores than did the IG (p 0.05). Conclusion Among participants with chronic LBP, three intervention therapies appear effective in reducing pain, diminishing disability, and enhancing quality of life. Also, combined therapy significantly improved pain and disability compared to the other two monotherapies; moreover, combined therapy and core muscle exercise provided similar benefits in terms of core muscle function after 12 weeks of intervention therapy.

Objectives: The present study aimed to determine the diagnostic value of sonographic signs in patients who have experienced an acute injury of the anterior talofibular ligament (ATFL), and provide diagnostic evidence for improving the classification of ATFL injuries. Methods: We retrospectively analyzed a total of 158 ATFL injuries, confirmed by surgery or magnetic resonance imaging (MRI), in 157 patients (one patient had bilateral ankle injury). A group of senior radiologists, along with two junior radiologists, identified the direct and indirect sonographic signs of ATFL injuries on ultrasound (US) images, and determined the ATFL injury classification. We then compared the diagnostic accuracy of the ATFL injury classifications, as well as the consistency of sonographic sign identification, between the senior radiologist group and the two junior radiologists. The sonographic signs identified by the senior radiologist group were used as the standard by which we analyzed the diagnostic efficacy of each sonographic sign for ATFL injury classification. Results: The diagnostic accuracy for complete ATFL tears was 88.5 % in the senior radiologist group, which was higher than that for the two junior radiologists (72.3 % and 67.7 %). Compared to the senior radiologist group, the consistency between the two junior radiologists in identifying all sonographic signs of ATFL injuries was low (kappa value 80 %. Direct sonographic signs were further combined with indirect sonographic signs to improve the diagnostic specificity and positive predictive value for the diagnosis of ATFL injuries. Conclusions: High-frequency US is the first choice for the diagnosis of ATFL injuries; however, radiologists with different levels of experience may classify ATFL injuries differently. Refined sonographic signs, especially ligament tension, clarity, and continuity, are helpful in the classification and diagnosis of ATFL injuries and provide guidance for the treatment and management of ankle injuries in clinical practice.

ABSTRACT Introduction Lung adenocarcinoma (LUAD) is one of the major histopathological types of non‐small cell lung cancer (NSCLC), including solid, acinar, lepidic, papillary and micropapillary subtypes. Increasing evidence has shown that micropapillary LUAD is positively associated with a higher percentage of driver gene mutations, a higher incidence of metastasis and a poorer prognosis, while lepidic LUAD has a relatively better prognosis. However, the novel genetic change and its underlying mechanism in the progression of micropapillary LUAD have not been exactly determined. Methods A total of 181 patients with LUAD who underwent surgery at the First Affiliated Hospital of Huzhou University from January 2020 to December 2022 were enrolled. Three predominant lepidic and three predominant micropapillary LUAD tissue samples were carried out using whole‐exome sequencing. Comprehensive analysis of genomic variations and the difference between lepidic and micropapillary LUAD was performed. In addition, the TMEM229A Q200del mutation was verified using our cohort and TCGA‐LUAD datasets. The correlations between the TMEM229A Q200del mutation and the clinicopathological characteristics of patients with LUAD were further analyzed. The functions and mechanisms of TMEM229A Q200del on NSCLC cell proliferation and migration were also determined. Results The frequency of genomic changes in patients with micropapillary LUAD was higher than that in patients with lepidic LUAD. Mutations in EGFR, ATXN2, C14orf180, MUC12, NOTCH1, and PKD1L2 were concomitantly detected in three predominant micropapillary and three predominant lepidic LUAD cases. The TMEM229A Q200del mutation was only mutated in lepidic LUAD. Additionally, the TMEM229A Q200del mutation had occurred in 16 (8.8%) patients, and not found TMEM229A R76H and M346T mutations in our cohort, while TMEM229A mutations (R76H, M346T, and Q200del) occurred only in 1.0% of the TCGA‐LUAD cohort. Further correlation analysis between the TMEM229A Q200del mutation and clinicopathological characteristics suggested that a lower frequency of the Q200del mutation was significantly associated with positive lymph node metastasis, advanced TNM stage, positive cancer thrombus, and pathological features. Finally, overexpression of TMEM229A Q200del suppressed NSCLC cell proliferation and migration in vitro. Mechanistically, overexpression of TMEM229A and TMEM229A Q200del both reduced the expression level of phosphorylated (p)‐ERK and p‐AKT (Ser473), and the reduced protein level of p‐ERK in the TMEM229A Q200del group was more pronounced compared to the TMEM229A group. Conclusion Our results demonstrated that the TMEM229A Q200del mutant may play a protective role in the progression of LUAD via inactivating ERK pathway, providing a potential therapeutic target in LUAD.

Objective: This study aimed to analyze research on anxiety disorders using VOSviewer and CiteSpace to identify research hotspots and future directions. Methods: We conduct ed a comprehensive search on the Web of Science Core Collection (WoSCC) for relevant studies about anxiety disorders published within the past two decades (from 2004 to 2024). VOSviewer and CiteSpace were mainly used to analyze the authors, institutions, countries, publishing journals, reference co-citation patterns, keyword co-occurrence, keyword clustering, and other aspects to construct a knowledge atlas. Results: A total of 22,267 publications related to anxiety disorders were retrieved. The number of publications about anxiety disorders has generally increased over time, with some fluctuations. The United States emerged as the most productive country, with Harvard University identified as the most prolific institution and Brenda W. J. H. Penninx as the most prolific author in the field. Conclusion: This research identified the most influential publications, authors, journals, institutions, and countries in the field of anxiety research. Future research directions are involved advanced treatments based on pharmacotherapy, psychotherapy and digital interventions, mechanism exploration to anxiety disorders based on neurobiological and genetic basis, influence of social and environmental factors on the onset of anxiety disorders.

Microbially-mediated arsenic biotransformation plays a pivotal role in the biogeochemical cycling of arsenic; however, the presence of arsenic biotransformation genes (ABGs) in urban dust remains unclear. To investigate the occurrence and spatiotemporal distributions of ABGs, a total of one hundred and eighteen urban dust samples were collected from different districts of Xiamen city, China in summer and winter. Although inorganic arsenic species, including arsenate [As(V)] and arsenite [As(III)], were found to be predominant, the methylated arsenicals, particularly trimethylarsine oxide [TMAs(V)O] and dimethylarsenate [DMAs(V)], were detected in urban dust. Abundant ABGs were identified in urban dust via AsChip analysis (a high-throughput qPCR chip for ABGs), of which As(III) S-adenosylmethionine methyltransferase genes (arsM), As(V) reductase genes (arsC), As(III) oxidase genes (aioA), As(III) transporter genes (arsB), and arsenic-sensing regulator genes (arsR) were the most prevalent, collectively constituting more than 90 % of ABGs in urban dust. Microbes involved in arsenic methylation were assigned to bacteria (e.g., Actinomycetes and Alphaproteobacteria), archaea (e.g., Halobacteria), and eukaryotes (e.g., Chlamydomonadaceae) in urban dust via the arsM amplicon sequencing. Temperature, a season-dependent environmental factor, profoundly affected the abundance of ABGs and the composition of microbes involved in arsenic methylation. This study provides new insights into the presence of ARGs within the urban dust.

BackgroundThe relationship between the levels of high-density lipoprotein (HDL) and bone mineral density (BMD) is controversial. Furthermore, the specific role of apolipoprotein A1 (APOA1), a primary HDL component, in regulating BMD remains unclear. This study aimed to elucidate the correlation between APOA1 levels and lumbar BMD in patients with osteoporotic fracture (OPF) for novel insights into potential therapeutic strategies against osteoporosis.MethodsThis study included 587 OPF patients enrolled at the Kunshan Hospital, Affiliated with Jiangsu University between January 2017 and July 2022. The patient’s serum APOA1 levels were determined, followed by the assessment of lumbar BMD and C-terminal telopeptide of type I collagen (β-CTX) as outcome variables. The association of APOA1 levels with lumbar BMD and β-CTX was assessed via Generalized Estimating Equations (GEE) and spline smoothing plot analyses. A generalized additive model (GAM) helped ascertain non-linear correlations. Moreover, a subgroup analysis was also conducted to validate the result’s stability.ResultsIt was observed that APOA1 levels were positively correlated with lumbar BMD (β = 0.07, 95% CI: 0.02 to 0.11, p = 0.0045), indicating that increased APOA1 levels were linked with enhanced lumbar BMD. Furthermore, APOA1 levels were negatively related to β-CTX (β = −0.19, 95% CI: −0.29 to −0.09, p = 0.0003), suggesting APOA1 might reduce osteolysis. In addition, these findings were robustly supported by subgroup and threshold effect analyses.ConclusionThis study indicated that increased APOA1 levels were correlated with enhanced lumbar BMD and decreased osteolysis in OPF patients. Therefore, APOA1 may inhibit osteoclast activity to prevent further deterioration in osteoporotic patients. However, further research I warranted to validate these conclusions and elucidate the underlying physiologies.

Introduction Reducing neonatal deaths in premature infants in low- and middle-income countries is key to reducing global neonatal mortality. International neonatal networks, along with patient registries of premature infants, have contributed to improving the quality of neonatal care; however, the involvement of low-to-middle-income countries was limited. This project aims to form an international collaboration among neonatal networks in Asia (AsianNeo), including low-, middle- and high-income countries (or regions). Specifically, it aims to determine outcomes in sick newborn infants, especially very low birth weight (VLBW) infants or very preterm infants, with a view to improving the quality of care for such infants.Methods and analysis Currently, AsianNeo comprises nine neonatal networks from Indonesia, Japan, Malaysia, Philippines, Singapore, South Korea, Sri Lanka, Taiwan and Thailand. AsianNeo will undertake the following four studies: (1) institutional questionnaire surveys investigating neonatal intensive care unit resources and the clinical management of sick newborn infants, with a focus on VLBW infants (nine countries/regions); (2) a retrospective cohort study to describe and compare the outcomes of VLBW infants among Asian countries and regions (four countries/regions); (3) a prospective cohort study to develop the AsianNeo registry of VLBW infants (six countries/regions); and (4) implementation and evaluation of educational and quality improvement projects in AsianNeo countries and regions (nine countries/regions).Ethics and dissemination The study protocol was approved by the Research Ethics Board of the National Center for Child Health and Development, Tokyo, Japan (reference number 2020–244, 2022–156). The study findings will be disseminated through educational programmes, quality improvement activities, conference presentations and medical journal publications.