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Background In recent years, physical impairment (PI) combined with cognitive impairment (CI) is a common comorbidity in the elderly. An early detection of PI combined with CI in the elderly and timely interventions may help to improve the quality of life of the elderly and reduce the burden on their families and society. However, relevant studies on the comorbidity of PI and CI in the elderly and its influencing factors have been rarely reported. Objective To observe the clinical characteristics of the comorbidity of PI and CI in the elderly and the influencing factors. Methods Elderly patients hospitalized in Peking University People's Hospital from September 2018 to November 2019 were selected. A total of eligible 244 subjects meeting the inclusion criteria were surveyed for the physical function and cognitive function using the Short Physical Performance Battery (SPPB) and the Mini-mental State Examination (MMSE), respectively. PI was diagnosed with lower than 10 points of the SPPB, and CI was diagnosed with lower than 27 points of the MMSE. Patients were divided into non-PI+non-CI, PI+non-CI, non-PI+CI, PI+CI. Social demographic, anthropometric, laboratory examination and other indicators of patients were collected, and Logistic regression analysis was used to explore the influencing factors for PI combined with CI in the elderly. Results Among the 244 patients, there were 102 (41.80%), 64 (26.23%), 26 (10.66%) and 52 (21.31%) cases of non-PI+non-CI, PI+non-CI, non-PI+CI and PI+CI, respectively. Multivariate binary Logistic regression analysis showed that compared with non-PI+non-CI cases, age (P

Abstract Background Medical device-related pressure injures (MDRPIs) are common in critically ill patients and associated with negative clinical outcomes and elevated healthcare expenses. We aim to estimate worldwide incidence of MDRPI and explore associated factors through systemic review and meta-analysis. Methods The PubMed, Web of Science, Cochrane Library, and Ovid EMBASE databases were systematically queried to identify relevant studies published from Jan 1, 2010 up until June 30, 2024. Studies were included if they provided data on the incidence or prevalence of MDRPI. Random-effect models were utilized to calculate the overall or domain-specific aggregated estimates of MDRPI. A meta-regression analysis was additionally performed to investigate the heterogeneity among studies. Results We included 28 observational studies on 117,624 patients in the meta-analysis. The overall incidence of MDRPI was 19.3% (95% confidence interval (CI) 13.5–25.2%). The incidence of MDRPI in Europe, North America, Asia, South America, and Oceania was 17.3% (95% CI 12.7–21.9%), 3.6% (95% CI 0.0–8.5%), 21.9% (95% CI 14.3–29.6%), 48.3% (95% CI 20.8–75.7%), and 13.0% (95% CI 5.0–21.1%), respectively (p

Abstract The rail profile milling process allows considerable thickness to be removed in a single pass. However, the residual waviness formation law after milling and its subsequent effect on rail performance remains uncertain. In this paper, the wavelength and wave height of the residual waviness are identified as the key characteristics. The relationship between milling speed and residual waviness is determined, and a numerical model of the residual waviness formed on the surface after milling is established based on the commonly used three milling speeds of 300, 600, and 1000 m/h, and its accuracy is verified using the parameters of the residual waviness detected by the milling experiments. A three-dimensional finite element analysis model of wheel-rail contact was employed to analyze the contact stresses and low fatigue cycles at a wheel load of 11.5 tons with no residual waviness on the rail profile surface and with three types of residual waviness, respectively. The results show that the residual waviness changes the wheel-rail contact position and the morphology of the contact area, reduces the maximum contact stress and increases the strain fatigue cycles. The application of elevated milling speeds reduces the wheel-rail contact stresses after milling, thereby increasing the low fatigue cycles.

Abstract Zika virus, a mosquito-borne arbovirus, has repeatedly caused large pandemics with symptoms worsening from mild and self-limiting diseases to Guillain–Barré syndrome in adults and fetal microcephaly in newborns. In recent years, Zika virus diseases have posed a serious threat to human health. The shortage of susceptible small animal models makes it difficult to study pathogenic mechanisms and evaluate potential therapies for Zika virus infection. Therefore, we chose immunocompromised mice (AG129 mice) deficient in IFN-α/β and IFN-γ receptors, which can abolish the innate immune system that prevents Zika virus infection early. AG129 mice were infected with the Zika virus, and this mouse model exhibited replication dynamics, tissue tropism, pathological lesion and immune activation of the Zika virus. Our results suggest that the inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in AG129 mice. By testing the potential antiviral drug favipiravir, several critical indicators, including replication dynamics and survival rates, were identified in AG129 mice after Zika virus infection. It is suggested that the model is reliable for drug evaluation. In brief, this model provides a potential platform for studies of the infectivity, virulence, and pathogenesis of the Zika virus. Moreover, the development of an accessible mouse model of Zika virus infection will expedite the research and deployment of therapeutics and vaccines.

Abstract. Background:. Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid (GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods:. We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 (E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results:. GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions:. GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Abstract Neoadjuvant therapy (NAT) is an important treatment for patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC), but neoadjuvant resistance affects the overall treatment outcome. Therefore, it is particularly important to accurately screen the population for NAT and explore the mechanism of resistance. Usually, different chemotherapy regimens cause different drug resistance mechanisms. Prior to combining immunotherapy with chemotherapy, extensive research has been conducted on previous drug resistance mechanisms. Currently, the mainstream NAT for ESCC involves chemotherapy combined with immunotherapy. We have witnessed the remarkable effect of this combination therapy; however, there are still a considerable number of patients whose tumor tissues show no change or even progress after NAT, and their drug resistance mechanisms remain unclear. Hence, we aim to identify relevant evidence that can distinguish and predict the effectiveness of NAT from a clinical perspective in order to provide a clinical basis for future screening of suitable populations for NAT and discovery of drug resistance mechanisms. This study is based in China's high incidence area of esophageal cancer, where enrolled patients all receive the current mainstream NAT regimen resulting in more reliable outcomes.

Abstract Background High-altitude cerebral edema (HACE) is considered an end-stage acute mountain sickness (AMS) that typically occurs in people after rapid ascent to 2500 m or more. While hypoxia is a fundamental feature of the pathophysiological mechanism of HACE, emerging evidence suggests that inflammation serves as a key risk factor in the occurrence and development of this disease. However, little is known about the molecular mechanism underlying their crosstalk. Methods A mouse HACE model was established by combination treatment with hypobaric hypoxia exposure and lipopolysaccharides (LPS) stimulation. Lactylated-proteomic analysis of microglia was performed to reveal the global profile of protein lactylation. Molecular modeling was applied to evaluate the 3-D modeling structures. A combination of experimental approaches, including western blotting, quantitative real-time reverse transcriptionpolymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA), confocal microscopy and RNA interference, were used to explore the underlying molecular mechanisms. Results We found that hypoxia exposure increased the lactate concentration and lactylation in mouse HACE model. Moreover, hypoxia aggravated the microglial neuroinflammatory response in a lactate-dependent manner. Global profiling of protein lactylation has shown that a large quantity of lysine-lactylated proteins are induced by hypoxia and preferentially occur in protein complexes, such as the NuRD complex, ribosome biogenesis complex, spliceosome complex, and DNA replication complex. The molecular modeling data indicated that lactylation could affect the 3-D theoretical structure and increase the solvent accessible surface area of HDAC1, MTA1 and Gatad2b, the core members of the NuRD complex. Further analysis by knockdown or selectively inhibition indicated that the NuRD complex is involved in hypoxia-mediated aggravation of inflammation. Conclusions These results revealed a comprehensive profile of protein lactylation in microglia and suggested that protein lysine lactylation plays an important role in the regulation of protein function and subsequently contributes to the neuroinflammatory response under hypoxic conditions.

Abstract Telemedicine and video-based diagnosis have raised significant concerns regarding the protection of facial privacy. Effective de-identification methods require the preservation of diagnostic information related to normal and pathological facial movements, which play a crucial role in the diagnosis of various movement, neurological, and psychiatric disorders. In this work, we have developed FaceMotionPreserve , a deep generative model-based approach that transforms patients’ facial identities while preserving facial dynamics with a novel face dynamic similarity module to enhance facial landmark consistency. We collected test videos from patients with Parkinson’s disease recruited via telemedicine for evaluation of model performance and clinical applicability. The performance of FaceMotionPreserve was quantitatively evaluated based on neurologist diagnostic consistency, critical facial behavior fidelity, and correlation of general facial dynamics. In addition, we further validated the robustness and advancements of our model in preserving medical information with clinical examination videos from a different cohort of patients. FaceMotionPreserve is applicable to real-time integration, safeguarding facial privacy while retaining crucial medical information associated with facial movements to address concerns in telemedicine, and facilitating safer and more collaborative medical data sharing.

Abstract The Qinghai-Tibet Plateau is a valuable genetic resource pool, and the high-altitude adaptation of Tibetan pigs is a classic example of the adaptive evolution of domestic animals. Here, we report the presence of Darwinian positive selection signatures in Tibetan pigs (TBPs) using 348 genome-wide datasets (127 whole-genome sequence datasets (WGSs) and 221 whole-genome single-nucleotide polymorphism (SNP) chip datasets). We characterized a high-confidence list of genetic signatures related response to high-altitude adaptation in Tibetan pigs, including 4,598 candidate SNPs and 131 candidate genes. Functional annotation and enrichment analysis revealed that 131 candidate genes are related to multiple systems and organs in Tibetan pigs. Notably, eight of the top ten novel genes, RALB, NBEA, LIFR, CLEC17A, PRIM2, CDH7, GK5 and FAM83B, were highlighted and associated with improved adaptive heart functions in Tibetan pigs high-altitude adaptation. Moreover, genome-wide association analysis revealed that 29 SNPs were involved in 13 candidate genes associated with at least one adaptive trait. In particular, among the top ten candidate genes, CLEC17A is related to a reduction in hemoglobin (HGB) in Tibetan pigs. Overall, our study provides a robust SNP/gene list involving genetic adaptation for Tibetan pig high-altitude adaptation, and it will be a valuable resource for future Tibetan pig studies.

Abstract This research delves into the transfer and loss of energy in a discrete mass when subjected to forced vibration. Using discrete element method (DEM), we analyzed the dynamic behavior of regular spherical granular assemblies and the energy distribution characteristics under different excitation frequencies and reduced accelerations. Moreover, the energy transfer and dissipation process of granular assemblies under different vibration states are studied using an experimental method. The results show that the granular assemblies will produce collision energy dissipation, thermal energy dissipation, acoustic energy dissipation and other forms of energy dissipation in the forced vibration state and the proportion of different energy dissipation under different excitation is given. The collision and friction of granular assemblies are the key to affecting other forms of energy dissipation. When the excitation increases, the energy dissipation forms are generated inside the granular assemblies, and the proportion of collision energy dissipation of the granular assemblies increases. The acoustic energy above 20 kHz occupies the main part of the acoustic energy dissipation. Thermal energy consumption always exists, which takes a long time to play a role. The granular also have other forms of energy loss, which is hard to be measured, including Rayleigh waves generated by granular collision. In this study, the relationship between the forced vibration state of the granular assemblies and the energy loss distribution is established. Various types of energy transfer and conversion distribution which further enriches the energy dissipation of discrete element calculation of the granular assemblies is discussed and provides a reference for the energy loss analysis of the granular assemblies.

Abstract Background This systematic study aims to assess the global epidemiologic, economic, and humanistic burden of illness associated with all types of hereditary angioedema. Methods A systematic search for articles reporting the epidemiologic, economic, and humanistic burden associated with patients with HAE was conducted using English and Chinese literature databases from the inception to May 23, 2022. The selected studies were assessed for their quality and risk of bias. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022352377). Results In total, 65 articles that met the search inclusion criteria reported 10,310 patients with HAE, of whom 5861 were female patients. Altogether, 4312 patients (81%) and 479 patients (9%) had type 1 and type 2 HAE, respectively, whereas 422 patients (8%) had HAE-normal C1-INH. The overall prevalence of all types of HAE was between 0.13 and 1.6 cases per 100,000. The mean or median delay from the first onset of a symptom of HAE to confirmed diagnosis ranged from 3.9 to 26 years. The estimated risk of death from asphyxiation was 8.6% for patients with HAE. Hospitalization, medication, unnecessary surgeries, doctor visits, specialist services, and nursing costs are direct expenses that contribute to the growing economic burden. The indirect cost accounted mostly due to missing work ($3402/year) and loss of productivity ($5750/year). Furthermore, impairment of QoL as reported by patient-reported outcomes was observed. QoL measures identified depression, anxiety, and stress to be the most common symptoms for adult patients and children. Conclusion This study highlights the importance of early diagnosis and the need for improving awareness among health care professionals to reduce the burden of HAE on patients and society.

Background The global prevalence of low back pain is gradually increasing, and it is the main cause of disability, sick leave, and unemployment, posing a heavy burden on individuals and society. Assessing the degree of disability in patients with chronic low back pain is crucial for evaluating the efficacy of clinical interventions and clinical epidemiology. The Roland-Morris Disability Questionnaire (RMDQ) is currently the main tool for evaluating disability in patients with low back pain, but the applicability of its measurement performance in the Chinese population remains unclear. Objective To evaluate the applicability of RMDQ in the Chinese population with low back pain and provide evidence for clinical practice and research application. Methods CNKI, Wanfang Data Knowledge Service Platform, SinoMed, PubMed, Embase and Web of Science were searched from inception to 2023-10-01, to establish a literature base for the performance of the low back pain scale, and then select research on the measurement performance of RMDQ from it. The measurement performance of the RMDQ scale was evaluated according to the COSMIN system evaluation guidelines, and the evidence evaluation level was used to grade the evidence. Results A total of six RMDQ documents were included, with insufficient methodological quality for RMDQ content validity and adequate measurement performance. The quality of internal consistency methodology was very good with uncertainty and measurement performance was adequate; the methodological quality of retesting was uncertain, and the measurement performance was sufficient; the methodological quality of measurement error was uncertain, and the measurement performance was sufficient; the methodological quality of criterion validity was uncertain, and the measurement performance was insufficient; hypothesis testing methodological quality was very good with uncertain, and the measurement performance was sufficient and uncertain; the quality of reactivity methodology was very good, with sufficient and insufficient, while the measurement performance was sufficient with insufficient. According to the GRADE evidence quality rating results, there is low quality evidence to prove uncertainty in content validity, and moderate quality evidence to prove sufficient retesting reliability and internal consistency; there is sufficient evidence of low quality to prove the measurement error and reactivity. There is very low quality evidence of insufficient calibration validity when using the Oswestry Dysfunction Index (ODI) and the Visual Analog Scale (VAS) as calibrators; hypothesis testing had moderate quality evidence of uncertainty. Conclusion The methodological quality of the RMDQ scale is not high, with acceptable measurement performanceand low quality of evidence, and needs to be used cautiously in clinical practice or trials of low back pain in China. Although there is sufficient evidence of moderate quality to prove the reliability and internal consistency of retesting, the research content and methods are not standardized. In future research, attention should be paid to standardization to more accurately assess its applicability in the Chinese population.

Abstract Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide, and the identification of novel treatment targets and prognostic biomarkers is urgently needed because of its unsatisfactory prognosis. Regulator of G-protein signaling 19 (RGS19) is a multifunctional protein that regulates the progression of various cancers. However, the specific function of RGS19 in HCC remains unclear. The expression of RGS19 was determined in clinical HCC samples. Functional and molecular biology experiments involving RGS19 were performed to explore the potential mechanisms of RGS19 in HCC. The results showed that the expression of RGS19 is upregulated in HCC tissues and is significantly associated with poor prognosis in HCC patients. RGS19 promotes the proliferation and metastasis of HCC cells in vitro and in vivo. Mechanistically, RGS19, via its RGS domain, stabilizes the MYH9 protein by directly inhibiting the interaction of MYH9 with STUB1, which has been identified as an E3 ligase of MYH9. Moreover, RGS19 activates β-catenin/c-Myc signaling via MYH9, and RGS19 is also a transcriptional target gene of c-Myc. A positive feedback loop formed by RGS19, MYH9, and the β-catenin/c-Myc axis was found in HCC. In conclusion, our research revealed that competition between RGS19 and STUB1 is a critical mechanism of MYH9 regulation and that the RGS19/MYH9/β-catenin/c-Myc feedback loop may represent a promising strategy for HCC therapy.

Objective To investigate whether nitrazepam can increase the accuracy of RigiScan measurement of nocturnal penile tumescence and rigidity （NPTR） by improving the sleep quality of patients. Methods All participants received NPTR measurement for two consecutive nights. In Trial 1， 125 normal volunteers were randomly assigned into the control group （n = 68） and experimental group （n = 57）. They took either a placebo or 10 mg of nitrazepam before NPTR testing on the second night to observe the effect of nitrazepam on nocturnal penile erections in the normal population. In Trial 2， 128 patients with erectile dysfunction were randomly assigned into the control group （n = 64） and experimental group （n = 64）. They took either a placebo or 10 mg of nitrazepam before NPTR testing to observe the effect of nitrazepam on NPTR detection parameters including effective erection times （EEE）， total erection duration （TED）， erection duration with erection rigidity≥60% （D60）， average erection rigidity （AER）， average erection tumescence circumference （AET）， rigidity activity unit （RAU） and tumescence activity unit （TAU） at the tip and base of the penis and the normal erection rates. Results In Trial 1， there were no statistically significant differences in NPTR parameters and normal rates between two groups on the second night （all P > 0.05）. The Richards-Campbell Sleep Questionnaire （RCSQ） score in the experimental group was higher than that in the control group （P < 0.001）. In Trial 2， NPTR parameters （D60tip， D60base， AERbase， RAUtip， TAUtip） on the first night were lower compared to those on the second night in the control group （all P < 0.05）， and there were no significant differences in normal erection rates （67.2% vs. 78.1%， P = 0.065）. Except for AETtip （7.85（6.83，8.98） cm vs. 8.10（7.50，8.90） cm， P = 0.014）， there were no statistically significant differences in NPTR parameters and normal erection rates between two nights in the experimental group （all P > 0.05）. In comparison between two groups， the parameters on the first night （EEE， D60tip， RAUtip and TAUtip）and those on the second night （EEE， D60tip， D60base， TED， RAUtip， RAUbase， TAUtip and TAUbase） in the experimental group were lower than those in the control group （all P < 0.05）. No significant difference was observed in the normal erection rates on the first night between two groups （67.2% vs. 65.6%， P = 0.852）， and the normal erection rate on the second night in the experimental group was lower than that in the control group （78.1% vs. 57.8%， P = 0.014）. In the experimental group， the RCSQ scores on two nights were higher compared to those in the control group， and the RCSQ scores on the first night were lower than those on the second night in both groups （both P < 0.05）. Conclusions NPTR measurement yields the first night effect. Nitrazepam can significantly inhibit the nocturnal penile erection. Improving sleep quality cannot eliminate the first night effect， whereas increase the false negative rate of NPTR measurement. Nitrazepam should be avoided in the NPTR measurement for patients with normal sleep， whereas it can be given for patients with sleep disorders or sleep difficulty after full consideration of the advantages and disadvantages.

Abstract Background Analyzing distance-dependent functional connectivity density (FCD) yields valuable insights into patterns of brain activity. Nevertheless, whether alterations of FCD in non-acute stroke patients are associated with the anatomical distance between brain regions remains unclear. This study aimed to explore the distance-related functional reorganization in non-acute stroke patients following left and right hemisphere subcortical lesions, and its relationship with clinical assessments. Methods In this study, we used resting-state fMRI to calculate distance-dependent (i.e., short- and long-range) FCD in 25 left subcortical stroke (LSS) patients, 22 right subcortical stroke (RSS) patients, and 39 well-matched healthy controls (HCs). Then, we compared FCD differences among the three groups and assessed the correlation between FCD alterations and paralyzed motor function using linear regression analysis. Results Our findings demonstrated that the left inferior frontal gyrus displayed distance-independent FCD changes, while the bilateral supplementary motor area, cerebellum, and left middle occipital gyrus exhibited distance-dependent FCD alterations in two patient subgroups compared with HCs. Furthermore, we observed a positive correlation between increased FCD in the bilateral supplementary motor area and the motor function of lower limbs, and a negative correlation between increased FCD in the left inferior frontal gyrus and the motor function of both upper and lower limbs across all stroke patients. These associations were validated by using a longitudinal dataset. Conclusions The FCD in the cerebral and cerebellar cortices shows distance-related changes in non-acute stroke patients with motor dysfunction, which may serve as potential biomarkers for predicting motor outcomes after stroke. These findings enhance our comprehension of the neurobiological mechanisms driving non-acute stroke. Trial registration All data used in the present study were obtained from a research trial registered with the ClinicalTrials.gov database (NCT05648552, registered 05 December 2022, starting from 01 January 2022).

Abstract Objective To develop a comprehensive compliance assessment scale for postoperative visual function rehabilitation in children with congenital cataracts and to assess its reliability and validity. Method Drawing on the Interactive Model of Health Behavior, we conducted a literature review and semi-structured interviews to create a pool of 36 items. The items underwent rigorous evaluation through the Delphi method, face validity checks, and item analysis, leading to a reduction to 18 items. To assess the scale's reliability and validity, we collected data from 225 parents of children with congenital cataracts. We employed SPSS version 25.0 for data analysis and evaluated construct validity using exploratory factor analysis, content validity, internal consistency reliability, and test–retest reliability. Results The compliance scale for postoperative visual function rehabilitation in children with congenital cataracts comprises 5 dimensions and 18 items. Exploratory factor analysis extracted 5 common factors, with a cumulative variance contribution rate of 68.178%. Item-level content validity index ranged from 0.730 to 1.000, and the content validity index of the scale was 0.963. The total Cronbach's alpha coefficient, split-half reliability, and test–retest reliability of the scale were 0.855, 0.778, and 0.859, respectively. Conclusions The compliance assessment scale for postoperative visual function rehabilitation in children with congenital cataracts demonstrates acceptable reliability and validity. It serves as a valuable reference for developing standardized nursing programs for these children in clinical practice.

Abstract Cuproptosis is a newly defined form of programmed cell death that relies on mitochondria respiration. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis and metastasis. However, whether cuproptosis-related lncRNAs are involved in the pathogenesis of diffuse large B cell lymphoma (DLBCL) remains unclear. This study aimed to identify the prognostic signatures of cuproptosis-related lncRNAs in DLBCL and investigate their potential molecular functions. RNA-Seq data and clinical information for DLBCL were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Cuproptosis-related lncRNAs were screened out through Pearson correlation analysis. Utilizing univariate Cox, least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analysis, we identified seven cuproptosis-related lncRNAs and developed a risk prediction model to evaluate its prognostic value across multiple groups. GO and KEGG functional analyses, single-sample GSEA (ssGSEA), and the ESTIMATE algorithm were used to analyze the mechanisms and immune status between the different risk groups. Additionally, drug sensitivity analysis identified drugs with potential efficacy in DLBCL. Finally, the protein–protein interaction (PPI) network were constructed based on the weighted gene co-expression network analysis (WGCNA). We identified a set of seven cuproptosis-related lncRNAs including LINC00294, RNF139-AS1, LINC00654, WWC2-AS2, LINC00661, LINC01165 and LINC01398, based on which we constructed a risk model for DLBCL. The high-risk group was associated with shorter survival time than the low-risk group, and the signature-based risk score demonstrated superior prognostic ability for DLBCL patients compared to traditional clinical features. By analyzing the immune landscapes between two groups, we found that immunosuppressive cell types were significantly increased in high-risk DLBCL group. Moreover, functional enrichment analysis highlighted the association of differentially expressed genes with metabolic, inflammatory and immune-related pathways in DLBCL patients. We also found that the high-risk group showed more sensitivity to vinorelbine and pyrimethamine. A cuproptosis-related lncRNA signature was established to predict the prognosis and provide insights into potential therapeutic strategies for DLBCL patients.

Abstract Objective The major challenge in routine endocervical curettage (ECC) among Human Papillomavirus (HPV) 16/18-positive patients is that only a small fraction benefit. Nevertheless, current reported models often overestimate the validity and necessity of ECC, making it difficult to improve benefits for patients. This research hypothesized that assessing paired boxed gene 1 methylation levels (PAX1m) and clinical characteristics could enhance the predictive accuracy of detecting additional high-grade squamous intraepithelial lesions or worse (HSIL +) through ECC that were not identified by colposcopy-directed biopsy (CDB). Methods Data from 134 women with HPV16/18 positivity undergoing CDB and ECC between April 2018 and April 2022 were collected and analyzed. Quantitative methylation-specific polymerase chain reaction (qMSP) was utilized to measure PAX1m, expressed as ΔCp. Univariate and multivariate regression analyses were conducted to screen variables and select predictive factors. A nomogram was constructed using multivariate logistic regression to predict additional HSIL + detected by ECC. The discrimination, calibration, and clinical utility of the nomogram were evaluated using receiver operating characteristic curves (ROC) and the calibration plot. Results Age (odds ratio [OR], 5.654; 95% confidence interval [CI], 1.131–37.700), cytology (OR, 24.978; 95% CI, 3.085–540.236), and PAX1 methylation levels by grade (PAX1m grade) (OR, 7.801; 95% CI, 1.548–44.828) were independent predictive factors for additional detection of HSIL + by ECC. In HPV16/18-positive women, the likelihood of additional detection of HSIL + through ECC increased with the severity of cytological abnormalities, peaking at 43.8% for high-grade cytological lesions. Moreover, when cytological findings indicated low-grade lesions, PAX1 methylation levels were positively correlated with the additional detection of HSIL + by ECC (P value

Background At present, Beijing has formulated a series of performance management policies for community health service centers, most of which focus on assessment and have not yet formed a performance management system. At the same time, there are still many problems in performance management considering the actual work of the centers. On the basis of the original internal performance appraisal system, this study improved the performance management in view of the existing problems, formed a set of performance management system applicable to the district community health service center, provided a reference for the community health service centers to establish a scientific performance management system in the future, and promoted the development of community health service work. Objective To explore the effect of performance management in community health service center. Methods In 2019, this group conducted a baseline survey on the current status of performance management in terms of center position setting, assessment indicators and weights, performance feedback and improvement in 18 community health service centers in Tongzhou District, Beijing. The Delphi expert consultation method was used to determine the evaluation indicators of the implementation effect of performance management, and the Internal Performance Management Manual of Community Health Service Centers (hereinafter referred to as the Manual), which contains 6 first-level indicators (number of services, service utilization, service quality, medical staff performance evaluation, patient satisfaction, and target management) and 34 second-level indicators, was finally determined. 2021, the evaluation of the application effect of the Manual was carried out (number of services, service utilization, service quality, medical staff performance evaluation, patient satisfaction, and target management) . Results The service quantity, service utilization and service quality of key work in 2020 were improved compared with those of the previous year, except for the family doctor contract rate and the real physical examination rate of the elderly, which were slightly lower than the regional average level, other indicators were higher than the regional level; performance management evaluation: Medical staff believed that the salary and workload were relatively matched and very matched increased by 29.8%; the cognition of center development goals, department development goals and individual work priorities increased by 15.6%, 13.2% and 2.6% respectively; the assessment indicators were in line with the actual work increased by 20.6%; reasonableness of index weight value and the secondary performance distribution of departments and stations increased by 19.4% and 8.3% respectively; the incentive that is strong increased by 18.3%; the performance improvement effect increased by 18.1% significantly; the overall satisfaction with performance management increased by 11.8%. Resident satisfaction: satisfaction with chronic disease management, children's health management, medical staff's technical level, and medical treatment results improved to varying degrees. Year-end assessment of district level: except for 1 center whose ranking remained unchanged, the rest of the centers were all improved. Salary: annual per capita incomes of on-the-job workers, doctors, nurses, and preventive and public health personnel increased by 5.2%, 7.6%, 8.4%, and 10.4% respectively, which was forty seven, eighty seven, forty four and thirty nine thousand higher than that of the whole region. Conclusion After the demonstration of community health service centers with different economic development levels, the application effect of the performance management system is remarkable, which improves the quantity and quality level of key work in the community, enhances the enthusiasm and service ability of medical staff, and then improves the satisfaction of patients, and it has certain promotion value. However, the number of centers that apply performance management system is limited and the time is short, so it is necessary to expand the application scope and continue to track the application situation in the future.

Chronic coronary disease (CCD) refers to chronic heart or vascular disease caused by insufficient blood flow into or out of the heart. The incidence and mortality rates of CCD are high, resulting in significant personal, economic, and societal burdens. In July 2023, the American Heart Association (AHA) and the American College of Cardiology (ACC), along with other academic organizations, jointly released the 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients with Chronic Coronary Disease. This guideline provides a on the evidence-based and patient-centered approach to comprehensive management of patients with CCD. It covers the epidemiology of CCD, patient assessment, diagnosis, risk stratification, treatment, management of special populations, patient follow-up, and related considerations. The guideline emphasizes the importance of a healthy diet, regular physical exercise, and tobacco avoidance for cardiovascular health. It also updates the recommendations for the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) and provides the latest evidence-based recommendations for clinical practice. This article provides a key interpretation of the management strategies outlined in the guideline, aiming to provide a basis for the development and update of relevant guidelines in China. The goal is to standardize and improve the specialized diagnosis and care for patients with CCD, with the ultimate aim of providing evidence-based guidance for clinical practice and improving the prognosis of patients with CCD.

Autophagy, a process that isolates intracellular components and fuses them with lysosomes for degradation, plays an important cytoprotective role by eliminating harmful intracellular substances and maintaining cellular homeostasis. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity for self-renewal that can give rise to a subset of tissues and therefore have potential in regenerative medicine. However, a variety of variables influence the biological activity of MSCs following their proliferation and transplantation in vitro. The regulation of autophagy in MSCs represents a possible mechanism that influences MSC differentiation properties under the right microenvironment, affecting their regenerative and therapeutic potential. However, a deeper understanding of exactly how autophagy is mobilized to function as well as clarifying the mechanisms by which autophagy promotes MSCs differentiation is still needed. Here, we review the current literature on the complex link between MSCs differentiation and autophagy induced by various extracellular or intracellular stimuli and the molecular targets that influence MSCs lineage determination, which may highlight the potential regulation of autophagy on MSCs’ therapeutic capacity, and provide a broader perspective on the clinical application of MSCs in the treatment of a wide range of diseases.

Abstract Purpose The duration of type 2 diabetes mellitus (T2DM) and blood glucose levels have a significant impact on the development of T2DM complications. However, currently known risk factors are not good predictors of the onset or progression of diabetic retinopathy (DR). Therefore, we aimed to investigate the differences in the serum lipid composition in patients with T2DM, without and with DR, and search for potential serological indicators associated with the development of DR. Methods A total of 622 patients with T2DM hospitalized in the Department of Endocrinology of the First Affiliated Hospital of Xi’an JiaoTong University were selected as the discovery set. One-to-one case–control matching was performed according to the traditional risk factors for DR (i.e., age, duration of diabetes, HbA1c level, and hypertension). All cases with comorbid chronic kidney disease were excluded to eliminate confounding factors. A total of 42 pairs were successfully matched. T2DM patients with DR (DR group) were the case group, and T2DM patients without DR (NDR group) served as control subjects. Ultra-performance liquid chromatography–mass spectrometry (LC–MS/MS) was used for untargeted lipidomics analysis on serum, and a partial least squares discriminant analysis (PLS-DA) model was established to screen differential lipid molecules based on variable importance in the projection (VIP) > 1. An additional 531 T2DM patients were selected as the validation set. Next, 1:1 propensity score matching (PSM) was performed for the traditional risk factors for DR, and a combined 95 pairings in the NDR and DR groups were successfully matched. The screened differential lipid molecules were validated by multiple reaction monitoring (MRM) quantification based on mass spectrometry. Results The discovery set showed no differences in traditional risk factors associated with the development of DR (i.e., age, disease duration, HbA1c, blood pressure, and glomerular filtration rate). In the DR group compared with the NDR group, the levels of three ceramides (Cer) and seven sphingomyelins (SM) were significantly lower, and one phosphatidylcholine (PC), two lysophosphatidylcholines (LPC), and two SMs were significantly higher. Furthermore, evaluation of these 15 differential lipid molecules in the validation sample set showed that three Cer and SM(d18:1/24:1) molecules were substantially lower in the DR group. After excluding other confounding factors (e.g., sex, BMI, lipid-lowering drug therapy, and lipid levels), multifactorial logistic regression analysis revealed that a lower abundance of two ceramides, i.e., Cer(d18:0/22:0) and Cer(d18:0/24:0), was an independent risk factor for the occurrence of DR in T2DM patients. Conclusion Disturbances in lipid metabolism are closely associated with the occurrence of DR in patients with T2DM, especially in ceramides. Our study revealed for the first time that Cer(d18:0/22:0) and Cer(d18:0/24:0) might be potential serological markers for the diagnosis of DR occurrence in T2DM patients, providing new ideas for the early diagnosis of DR.

Background Due to its unique advantages, virtual reality rehabilitation (VR) training has been widely used in the field of rehabilitation therapy, but there is a lack of study on its application efficacy in patients with sudden deafness and vertigo. Objective To observe the efficacy of coventional vestibular rehabilitation training and vestibular rehabilitation training assisted by VR technology in patients with sudden deafness and vertigo. Methods From January 2022 to January 2023, 84 patients with sudden deafness and vertigo were selected from the Department of Otolaryngology Head and Neck Surgery, First Hospital of Shanxi Medical University and randomly divided into the two groups, with 42 cases in each group. The control group was given drug therapy combined with coventional vestibular rehabilitation training, while the observation group was given vestibular rehabilitation training assisted by VR technology on the basis of drug therapy. The Dizziness Disorder Scale (DHI) and Hospital Anxiety and Depression Scale (HADS) were respectively used to evaluate the two groups before intervention, 7 and 14 days after the intervention. Results Finally 81 patients completed the trial, including 41 patients in the observation group and 40 patients in the control group. Group and time had interaction effects on DHI-Function (F), DHI-Emotion (E) and DHI-Physical (P) scores and total DHI score (P0.05) ; DHI sub-scores and total score in both groups after 7 and 14 days of intervention were lower than those before intervention (P0.05). HADS sub-scores and total score in both groups after 7 and 14 days of intervention were lower than those before intervention (P0.05) . Conclusion Vestibular rehabilitation training is effective for patients with sudden deafness and vertigo, and the vestibular rehabilitation training assisted by VR technology can obviously improve patients' balance disorders and quality of life.

Congenital muscular torticollis (CMT) is a more common childcare disease, which belongs to muscle-skeletal system diseases, and is more common in newborns. The disease is mainly due to congenital contracture due to chest locks, which leads to asymmetric head and neck. For such diseases, clear diagnosis and treatment in the early days is an important way to improve the prognosis of children. Compared with X-ray film, CT, and MRI, ultrasound examination has the advantages of low examination cost, short time, and no exposure to radiation during the examination. Moreover, ultrasound examination can provide an objective basis for the clinical diagnosis and prognosis evaluation of CMT children. This article reviews the latest research progress of conventional ultrasound, color Doppler ultrasound, and ultrasound elastography in the clinical diagnosis of CMT children and assisting in the formulation of treatment plans.

"Objective To search，organize,and summarize the best evidence of rehabilitation timing for patients after arthroscopic rotator cuff repair surgery, providing reference for clinical practice. Methods Databases and websites such as UpToDate, USC, AHQR, Cochrane Library, JBI Library, Embase, PubMed, China Biomedical Literature Database, CNKI, VIP, Wanfang, and the National Institute of Health and Care Extellence (NICE) were searched systematically. The types of literature retrieval included clinical decision-making, clinical practice guidelines, expert consensus, best evidence summary, and systematic evaluation/meta-analysis. The search period was from January 1, 2013 to January 1, 2023, and relevant literature on the timing of rehabilitation for patients undergoing arthroscopic rotator cuff repair surgery was collected. Two researchers independently conducted literature screening and methodological quality evaluation, extracted and summarized literature that met the standards, and formed the best evidence. Results A total of 11 articles were included, including 3 guidelines, 2 expert consensus, and 6 systematic evaluations. By summarizing and refining the evidence, a total of 5 aspects were formed, including the definition of early/delayed plans, fixed time, rehabilitation timing, exercise methods, and functional outcomes, with a total of 25 pieces of evidence. Conclusion This study summarizes the best evidence for rehabilitation timing after arthroscopic rotator cuff repair surgery. Clinical staff can intervene with patients based on the best evidence, choose the best timing for targeted rehabilitation plans, and adjust rehabilitation strategies in a timely manner to improve patients adaptability and promote rapid recovery."

Objective To compare the analgesic effects and safety of ultransound-guided thoracic paravertebral block (TPVB) and intercostal nerve block (INB) in patients with unilateral multiple rib fractures. Methods Patients with unilateral multiple rib fractures treated by surgery at the Fifth Affiliated Hospital of Xinjiang Medical University from January 2022 to June 2023 were selected. A total of 82 patients who met the inclusion and exclusion criteria were included,and divided into TPVB group (20 mL of ropivacaine 0.33% for TPVB after general anesthesia) and INB group (5 mL of ropivacaine 0.33% for INB after general anesthesia) by random number table method, with 41 patients in each group. The visual analog score (VAS) was used to assess patients pain, and the time and dosage of analgesics were recorded. The pulmonary and non-pulmonary complications within 72 hours after operation were observed. Results Kaplan-Meier curves showed that there was a statistically significant difference in first use time of analgesics between the two groups (χ2=6.125, P=0.013). The proportion of patients with analgesia demand in the TPVB group was significantly lower than that in the INB group within 24 hours after operation (19.51% vs 36.59%, χ2=4.895， P=0.027)and 48 hours after operation(41.46% vs 63.41%， χ2=3.961， P=0.047), and the total dose of analgesics used 〖LM〗in the TPVB group 25-48 hours after operation was significantly lower than that in the INB group ［(13.78±9.48) mg vs (26.20±12.31)mg, t=3.527, P＜0.01］. VAS scores at rest and during coughing at all time points after surgery significantly decreased in both groups (P＜0.01). At 6 and 18 hours postoperatively, the VAS score at rest in the TPVB group was lower than that in the INB group, and at 1, 6, and 18 hours postoperatively, the VAS score when coughing in the TPVB group was lower than that in the INB group, with statistically significant differences (P＜0.05). There was no statistically significant difference in the incidence of pulmonary and non-pulmonary complications between the two groups (P＞0.05). Conclusion Ultrasound-guided TPVB can effectively alleviate pain and reduce opioid consumption in patients with unilateral multiple rib fractures compared with INB."

Abstract Establish a new classification system of distal radius fracture based on computed tomographic (CT), and evaluate its reliability and reproducibility preliminarily, and provide a new theoretical reference for clinicians to use the clinical classification system. The imaging data and clinical data of 204 inpatients with distal radius fracture during 6 years from January 1, 2014 to January 1, 2019 in orthopaedic department were analyzed retrospectively and classified based on CT. Three observers evaluated the image data of 48 randomly selected cases based on CT at different time nodes of T1 and T2. Cohen's kappa was used to calculate the consistency. At the last follow-up, patients' Disabilities of the Arm, Shoulder and Hand (DASH), Patient Rated Wrist Evaluation (PRWE), and VAS scores were collected. Among 204 cases, there were 12 cases of type 1, including 6 cases of type 1-D, 4 cases of type 1-V and 2 cases of type 1-R. There were 6 cases of type 2, including 2 cases of type 2-DV, 2 cases of type 2-DR and 2 cases of type 2-VR. There were 186 cases of type 3, including 32 cases of type 3–0, 127 cases of type 3–1 and 27 cases of type 3–2. There was no significant difference in DASH, PRWE and VAS scores among all types (P > 0.05). The results of interobserver reproducibility were kappa = 0.985, ICC = 0.984 in the first evaluation, kappa = 0.986, ICC = 0.986 in the second evaluation. The results of intraobserver reproducibility were O1 = 0.991, O2 = 0.991, O3 = 0.989 respectively. The new classification system of distal radius fracture based on CT has theoretical and practical significance for incision selection, fracture reduction and internal fixation. 123 classification system is clear, comprehensive, easy to understand and remember. Moreover, it has higher interobserver reliability and intraobserver reproducibility than other systems reported at present.

Abstract Global climate change, with warming as its main feature, has altered the spatial-temporal evolution of factors such as precipitation and temperature that can cause meteorological disasters. The complex and changeable climate has led to frequent natural disasters, while the frequency and intensity of extreme climate events have also significantly increased, posing an enormous threat to societal production and human life. As the most important geoecological transitional zone of mainland China, the stability of agricultural production in China’s north–south transitional zone is crucial for ensuring food security under climate change. With the use of daily precipitation and potential evapotranspiration data from 1961 to 2018, this study focused on analysing disturbances such as extreme precipitation and drought disasters at different time scales during the winter wheat and summer maize growing seasons in the north–south transitional zone of China from an agricultural production perspective and attempted to answer the following questions: first, from an agricultural production perspective, what are the temporal and spatial distribution patterns of extreme precipitation and arid climate events in the north–south transitional zone? Second, which areas are at high risk of being disturbed by different types of meteorological disasters and require increased attention? The results indicated that (1) in terms of the overall temporal variation, the degree of extreme precipitation and drought stress faced by agricultural production in the region is decreasing. However, the temporal variation at each station in the north–south transitional zone was not completely consistent with the overall trend, and both increasing and decreasing trends were observed. The sites exhibiting an increase overlapped with typical regions of the north–south transitional zone to varying degrees, indicating that the typical regions represented not only theoretical potential risk areas under climate change but also suffered from meteorological disaster disturbances. (2) The precipitation distribution during the winter wheat growth period in the south–north transitional zone was uneven and varied significantly. High values of extreme precipitation indices during the winter wheat growth period were mainly concentrated in the southern part of the eastern section of the north‒south transitional zone. The precipitation distribution during the summer maize growth period significantly differed, with the highest amount of heavy rain and largest number of rainstorm days concentrated in the southeastern part of the north‒south transitional zone. The spatial distribution of the drought frequency in the north–south transitional zone, as indicated by the monthly standardized precipitation evapotranspiration index (SPEI1), showed that the areas with high total drought frequencies were mainly concentrated in northeast Jiangsu, southeast Henan, and north Anhui, which primarily experienced light drought. The central part of Jiangsu Province exhibited a high frequency of moderate drought, while southern Jiangsu Province and southwestern Shaanxi Province were prone to severe drought. Additionally, southeastern Hebei and eastern Henan were identified as areas with a high frequency of extreme drought. Finally, the central region of Sichuan Province was characterized by both severe and extreme drought conditions. Based on the SPEI12-derived spatial distribution of the drought frequency in the north–south transitional zone, the areas with a high total drought frequency were mainly concentrated in central and eastern Henan, southeast Shaanxi, southeast Shandong, and central Sichuan, which primarily experienced light to moderate drought. The northwestern part of Jiangsu, the southern part of Hebei, and the western part of Shandong are regions with a high frequency of severe drought, while the eastern part of Henan is an area with high frequencies of both severe and extreme drought. (3) High-value areas of extreme precipitation and drought disturbance in the north–south transitional zone overlapped with the edge of the transitional zone to varying degrees. Approximately 63.58% of the north‒south transitional zone of China was characterized by moderate or high stress levels, primarily concentrated along the southern boundary and central core area, and nearly 39.5% of all counties experienced two or more types of disaster stresses.

Abstract REBCO has been used extensively as coated conductors applied to superconducting magnets due to its exceptional superconducting properties. As a REBCO superconductor, YbBa2Cu3O7−y (Yb123) has a low melting temperature, making it suitable for use as an intermediate medium connector while preparing the superconducting joint. However, there is still uncertainty about the formation mechanism of Yb123 and the synthesis of this superconductor has not been fully understood. Therefore, this study systematically investigated the phase transformation process of Yb123 during heat treatment in flowing oxygen. The results indicated that Yb123 sample with the highest phase purity could be obtained by annealing at 927 °C or 937 °C but not in between, respectively. Furthermore, a quantitative phase analysis revealed that the sample annealed at 937 °C had a phase purity greater than 80 wt%. Additionally, a strong c-axis texture was observed in the bulk Yb123 superconductor prepared at 937 °C. Meanwhile, the superconducting results revealed that the bulk sample’s Tc was 89.9 K, and its self-field critical current densities at 4.2 K and 77 K were 1.3 × 105 A/cm2 and 5.0 × 103 A/cm2, respectively. Based on the results mentioned above, the phase transformation process and formation mechanism of Yb123 in flowing oxygen were elaborated.

Abstract This study aims to explore the correlation between the CT-L1 and L3 body composition parameters and analyze the relationship between L1 body composition and hematologic toxicity in luminal-type breast cancer patients undergoing neoadjuvant chemotherapy. Data from 140 luminal-type breast cancer patients who underwent surgical treatment after neoadjuvant chemotherapy were analyzed retrospectively. Spearman analysis was used to assess the correlation between CT-L1 and CT-L3 body composition parameters pre-neoadjuvant chemotherapy. Additionally, univariate and multivariate logistic regression analyses were performed to identify factors influencing hematologic toxicity. CT-L1 body composition parameters were positively correlated with CT-L3 body composition parameters in 34 patients. Severe hematological toxicity occurred in 46 cases among the patient cohort. A skeletal muscle index (SMI) of

Abstract To figure out how does SARS-CoV-2 affect sperm parameters and what influencing factors affect the recovery of sperm quality after infection? We conducted a prospective cohort study and initially included 122 men with SARS-CoV-2 infection. The longest time to track semen quality after infection is 112 days and 58 eligible patients were included in our study eventually. We subsequently exploited a linear mixed-effects model to statistically analyze their semen parameters at different time points before and after SARS-CoV-2 infection. Semen parameters were significantly reduced after SARS-CoV-2 infection, including total sperm count (211 [147; 347] to 167 [65.0; 258], P

Abstract Background Caspase Recruitment Domain-containing protein 9 (CARD9) expressed in myeloid cells has been demonstrated to play an antifungal immunity role in protecting against disseminated candidiasis. Hereditary CARD9 ablation leads to fatal disseminated candidiasis. However, the myeloid cell types and molecular mechanisms implicated in CARD9 protecting against disseminated candidiasis remain wholly elusive. Methods The role of CARD9 ablation in exacerbating disseminated candidiasis was determined in vivo and in vitro. The molecular mechanism by which CARD9 ablation promotes acute kidney injury in disseminated candidiasis was identified by RNA-sequencing analysis. The expression of mitochondrial proteins and ferroptosis-associated proteins were measured by Quantitative real-time PCR and western blot. Results CARD9 ablation resulted in a reduced proportion of myeloid-derived suppressor cells (MDSCs) and a substantially lower expression of solute carrier family 7 member 11 (SLC7A11) in the kidneys, which increased susceptibility to acute kidney injury and renal ferroptosis during disseminated Candida tropicalis (C. tropicalis) infection. Moreover, CARD9-deficient MDSCs were susceptible to ferroptosis upon stimulation with C. tropicalis, which was attributed to augmented mitochondrial oxidative phosphorylation (OXPHOS) caused by reduced SLC7A11 expression. Mechanistically, C-type lectin receptors (CLRs)-mediated recognition of C. tropicalis promoted the expression of SLC7A11 which was transcriptionally manipulated by the Syk-PKCδ-CARD9-FosB signaling axis in MDSCs. FosB enhanced SLC7A11 transcription by binding to the promoter of SLC7A11 in MDSCs stimulated with C. tropicalis. Mitochondrial OXPHOS, which was negatively regulated by SLC7A11, was responsible for inducing ferroptosis of MDSCs upon C. tropicalis stimulation. Finally, pharmacological inhibition of mitochondrial OXPHOS or ferroptosis significantly increased the number of MDSCs in the kidneys to augment host antifungal immunity, thereby attenuating ferroptosis and acute kidney injury exacerbated by CARD9 ablation during disseminated candidiasis. Conclusions Collectively, our findings show that CARD9 ablation enhances mitochondria-mediated ferroptosis in MDSCs, which negatively regulates antifungal immunity. We also identify mitochondria-mediated ferroptosis in MDSCs as a new molecular mechanism of CARD9 ablation-exacerbated acute kidney injury during disseminated candidiasis, thus targeting mitochondria-mediated ferroptosis is a novel therapeutic strategy for acute kidney injury in disseminated candidiasis.

The physiological activity facilitated by arbuscular mycorrhizal fungi (AMF) contributes to plants’ ability to tolerate drought. Nevertheless, it is unclear if AMF colonization affects the expression of genes in the host plant that encode antioxidant enzymes in the superoxide dismutase (SOD) family, which help alleviate drought stress in plants. Here, we conducted a pot trial to determine whether colonization by the AMF Rhizophagus irregularis improves drought resistance in Bombax ceiba. We comprehensively analyzed the SOD gene family and evaluated genome-wide expression patterns of SODs and SOD activity in AMF-colonized and non-mycorrhizal plants under simulated drought. We identified a total of 13 SODs in the genome of B. ceiba, including three FeSODs (BcFSDs), three MnSODs (BcMSDs), and seven Cu/ZnSODs (BcCSDs). Phylogenetic analysis based on binding domain revealed that SOD genes from B. ceiba and various other plant species can be divided into three separate groups, showing significant bootstrap values. Our examination of gene composition and patterns suggests that most BcSOD genes in these three subgroups are significantly conserved. Additionally, it was noted that hormones and stress-responsive cis-regulatory elements were found in all BcSOD promoters. Expression profiling by qRT-PCR demonstrated that AMF increased relative expression levels of Cu/Zn-SODs in both roots and shoots under drought stress, except for BcCSD3 in roots. Furthermore, AMF colonization increased the relative expression of BcMSD1a and BcMSD1b in roots, augmenting SOD activities and increasing ROS scavenging during drought. In general, this work offers molecular evidence in support of the beneficial effect of AMF colonization on drought tolerance in B. ceiba. It also elucidates the expression patterns of SOD genes, which will support efforts to optimize mycorrhizal seedling cultivation under stressful conditions.

Introduction Mild cognitive impairment (MCI) is an intermediate phase between normal cognitive ageing and dementia and poses a serious threat to public health worldwide; however, it might be reversible, representing the best opportunity for secondary prevention against serious cognitive impairment. As a non-pharmacological intervention for those patients, interventions that combine physical exercise and cognitive training, whether delivered simultaneously or sequentially, may have superior effects on various cognitive domains, including global cognition, memory, executive function and attention. The supportive evidence remains incomplete. This study aims to assess the effectiveness of a combined exercise and cognitive intervention in Chinese older adults with mild cognitive impairment (COGITO), empowered by digital therapy and guided by the Health Action Process Model and the Theory of Planned Behaviour (HAPA-TPB theory) in a home-based setting.Methods and analysis This study is a randomised controlled, assessor-blinded multi-centre study. Four parallel groups will include a total of 160 patients, receiving either a combined exercise and cognitive intervention, an isolated exercise intervention, an isolated cognitive intervention or only health education. These interventions will be conducted at least twice a week for 50 min each session, over 3 months. All interventions will be delivered at home and remotely monitored through RehabApp and Mini-programme, along with an arm-worn heart rate telemetry device. Specifically, supervisors will receive participants’ real-time training diaries, heart rates or other online monitoring data and then provide weekly telephone calls and monthly home visits to encourage participants to complete their tasks and address any difficulties based on their training information. Eligible participants are community-dwelling patients with no regular exercise habit and diagnosed with MCI. The primary outcome is cognitive function assessed by the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) and Community Screening Instrument for Dementia (CSI-D), with baseline and three follow-up assessments. Secondary outcomes include quality of life, physical fitness, sleep quality, intrinsic capacity, frailty, social support, adherence, cost-effectiveness and cost-benefit.Ethics and dissemination The study was approved by the Institutional Review Board of Peking University. Research findings will be presented to stakeholders and published in peer-reviewed journals and at provincial, national and international conferences.Trial registration number ChiCTR2300073900.

Abstract Spider silk proteins (spidroins) are particularly attractive due to their excellent biocompatibility. Spider can produce up to seven different types of spidroins, each with unique properties and functions. Spider minor ampullate silk protein (MiSp) might be particularly interesting for biomedical applications, as the constituent silk is mechanically strong and does not super‐contract in water, attributed to its amino acid composition. In this study, we evaluate the potential of recombinant nanoparticles derived from Araneus ventricosus MiSp as a protein delivery carrier. The MiSp‐based nanoparticles were able to serve as an effective delivery system, achieving nearly 100% efficiency in loading the model protein lysozyme, and displayed a sustained release profile at physiological pH. These nanoparticles could significantly improve the delivery efficacy of the model proteins through different administration routes. Furthermore, nanoparticles loaded with model protein antigen lysozyme after subcutaneous or intramuscular administration could enhance antigen‐specific immune responses in mouse models, through a mechanism involving antigen‐depot effects at the injection site, long‐term antigen persistence, and efficient uptake by dendritic cells as well as internalization by lymph nodes. These findings highlight the transnational potential of MiSp‐based nanoparticle system for protein drug and vaccine delivery.

Analogues of the hepatokine fibroblast growth factor 21 (FGF21) are in clinical development for type 2 diabetes and nonalcoholic steatohepatitis (NASH) treatment. Although their glucose-lowering and insulin-sensitizing effects have been largely unraveled, the mechanisms by which they alleviate liver injury have only been scarcely addressed. Here, we aimed to unveil the mechanisms underlying the protective effects of FGF21 on NASH using APOE*3-Leiden.CETP mice, a well-established model for human-like metabolic diseases. Liver-specific FGF21 overexpression was achieved in mice, followed by administration of a high-fat high-cholesterol diet for 23 weeks. FGF21 prevented hepatic lipotoxicity, accompanied by activation of thermogenic tissues and attenuation of adipose tissue inflammation, improvement of hyperglycemia and hypertriglyceridemia, and upregulation of hepatic programs involved in fatty acid oxidation and cholesterol removal. Furthermore, FGF21 inhibited hepatic inflammation, as evidenced by reduced Kupffer cell (KC) activation, diminished monocyte infiltration, and lowered accumulation of monocyte-derived macrophages. Moreover, FGF21 decreased lipid- and scar-associated macrophages, which correlated with less hepatic fibrosis as demonstrated by reduced collagen accumulation. Collectively, hepatic FGF21 overexpression limits hepatic lipotoxicity, inflammation, and fibrogenesis. Mechanistically, FGF21 blocks hepatic lipid influx and accumulation through combined endocrine and autocrine signaling, respectively, which prevents KC activation and lowers the presence of lipid- and scar-associated macrophages to inhibit fibrogenesis.

Background Schizophrenia often experience severe social discrimination throughout their entire survival period, resulting in self isolation or social isolation. Limited studies have been conducted on social isolation in young and middle-aged patients with schizophrenia in remission. Objective To describe the social isolation experience of young and middle-aged patients with schizophrenia in remission, aiming to provide reference for developing supportive intervention plans to alleviate the social isolation experience of this population. Methods A purposive sampling method was used to select young and middle-aged schizophrenia patients aged 18-59 who had been hospitalized at the Second Affiliated Hospital of Xinxiang Medical University and were willing to continue follow-up after discharge as the research subjects. From May to December 2022, a semi-structured in-depth interview was conducted face-to-face with the respondents, and the themes were summarized and extracted using content analysis method. Results A total of 18 young and middle-aged patients with schizophrenia in remission were included. By analyzing the interview data, a total of 3 themes and 8 sub themes were extracted, including the performance of social isolation in young and middle-aged patients with schizophrenia in remission (containing 2 subthemes of negative emotional experience and withdrawal between expectation and behavior) ; subjective reasons for social isolation in young and middle-aged patients with schizophrenia in remission (containing 2 subthemes of self isolation and self discrimination) , and the objective reasons for social isolation in young and middle-aged patients with schizophrenia in remission (containing 4 subthemes of social discrimination and passive containing, effects of adverse drug reactions, increased burden of living and care caused by mental illness, and the lack of social support) . Conclusion Young and middle-aged patients with schizophrenia in remission may experience social isolation due to impaired physical health, poor psychological status, and insufficient social support. Healthcare professionals should strengthen symptom management and psychological counseling for this population. The government and all sectors of society should actively guide positive perception of mental illness and provide certain social support; family support should be strengthened to help young and middle-aged patients with schizophrenia in remission reintegrate and adapt to society.

Objective To explore the predictive value of different machine learning models based on MRI radiomics combined with clinical features for histological grade of cervical squamous cell carcinoma. Methods Clinical data of 150 patients with cervical squamous cell carcinoma confirmed by pathological biopsy were retrospectively analyzed. They were randomly divided into the training set and validation set at a ratio of 4∶1. Features were extracted from the regions of interest of T2WI fat suppression sequence （FS-T2WI） and enhanced T1WI （delayed phase）. After dimensionality reduction and feature selection， logistic regression （LR）， support vector machine （SVM）， naïve Bayes （NB）， random forest （RF）， Light Gradient Boosting Machine （LightGBM）， K-nearest neighbor （KNN） were used to construct a radiomics model for predicting the histological grade of cervical squamous cell carcinoma. The area under the receiver operating characteristic （ROC） curve （AUC） was used to evaluate the predictive performance of the six models. Univariate and multivariate logistic regression analyses were performed to predict the independent risk factors， and a combined model of clinical and radiomics was established. The differences of each model were compared by AUC， and the clinical value of the model was evaluated by decision curve （DCA）. Results In the radiomics model， the LightGBM model had the largest AUC （0.910 in the training set， and 0.839 in the validation set）. The AUC of clinical features combined with LightGBM model was the largest （0.935 in the training set， and 0.888 in the validation set）， which was higher than those of clinical model （0.762 in the training set， and 0.710 in the validation set） and LightGBM radiomics model. Conclusions The LightGBM model has a high predictive value in the radiomics model. The combined model has the optimal DCA effect and the highest clinical net benefit. The combined prediction model combining radiomics and clinical features has good predictive value for cervical squamous cell carcinoma with low differentiation， providing a non-invasive and efficient method for clinical decision-making.

Abstract Background The treatment of spinal cord injury (SCI) has always been a significant research focus of clinical neuroscience, with inhibition of microglia-mediated neuro-inflammation as well as oxidative stress key to successful SCI patient treatment. Caffeic acid phenethyl ester (CAPE), a compound extracted from propolis, has both anti-inflammatory and anti-oxidative effects, but its SCI therapeutic effects have rarely been reported. Methods We constructed a mouse spinal cord contusion model and administered CAPE intraperitoneally for 7 consecutive days after injury, and methylprednisolone (MP) was used as a positive control. Hematoxylin–eosin, Nissl, and Luxol Fast Blue staining were used to assess the effect of CAPE on the structures of nervous tissue after SCI. Basso Mouse Scale scores and footprint analysis were used to explore the effect of CAPE on the recovery of motor function by SCI mice. Western blot analysis and immunofluorescence staining assessed levels of inflammatory mediators and oxidative stress-related proteins both in vivo and in vitro after CAPE treatment. Further, reactive oxygen species (ROS) within the cytoplasm were detected using an ROS kit. Changes in mitochondrial membrane potential after CAPE treatment were detected with 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide. Mechanistically, western blot analysis and immunofluorescence staining were used to examine the effect of CAPE on the SIRT1/PGC1α/DRP1 signaling pathway. Results CAPE-treated SCI mice showed less neuronal tissue loss, more neuronal survival, and reduced demyelination. Interestingly, SCI mice treated with CAPE showed better recovery of motor function. CAPE treatment reduced the expression of inflammatory and oxidative mediators, including iNOS, COX-2, TNF-α, IL-1β, 1L-6, NOX-2, and NOX-4, as well as the positive control MP both in vitro and in vivo. In addition, molecular docking experiments showed that CAPE had a high affinity for SIRT1, and that CAPE treatment significantly activated SIRT1 and PGC1α, with down-regulation of DRP1. Further, CAPE treatment significantly reduced the level of ROS in cellular cytoplasm and increased the mitochondrial membrane potential, which improved normal mitochondrial function. After administering the SIRT1 inhibitor nicotinamide, the effect of CAPE on neuro-inflammation and oxidative stress was reversed.On the contrary, SIRT1 agonist SRT2183 further enhanced the anti-inflammatory and antioxidant effects of CAPE, indicating that the anti-inflammatory and anti-oxidative stress effects of CAPE after SCI were dependent on SIRT1. Conclusion CAPE inhibits microglia-mediated neuro-inflammation and oxidative stress and supports mitochondrial function by regulating the SIRT1/PGC1α/DRP1 signaling pathway after SCI. These effects demonstrate that CAPE reduces nerve tissue damage. Therefore, CAPE is a potential drug for the treatment of SCI through production of anti-inflammatory and anti-oxidative stress effects. Graphical Abstract

Abstract. Background:. Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring's cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring's cognitive performance during adolescence and young adulthood in China. Methods:. We included 2531 adolescents aged 10–15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0–5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring's fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018). Results:. Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29–0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16–0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring's healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring's cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring's overall crystallized intelligence. Conclusions:. Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring's cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.

Abstract Background Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus. Methods HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-α-stimulated endothelial cells pretreated with HDL. Results ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = − 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p

Abstract Background Although hepatitis B virus (HBV) infection is a major risk factor for hepatic cancer, the majority of HBV carriers do not develop this lethal disease. Additional molecular alterations are thus implicated in the process of liver tumorigenesis. Since phosphatase and tensin homolog (PTEN) is decreased in approximately half of liver cancers, we investigated the significance of PTEN deficiency in HBV-related hepatocarcinogenesis. Methods HBV-positive human liver cancer tissues were checked for PTEN expression. Transgenic HBV, Alb-Cre and Pten fl/fl mice were inter-crossed to generate WT, HBV, Pten −/− and HBV; Pten −/− mice. Immunoblotting, histological analysis and qRT-PCR were used to study these livers. Gp73 −/− mice were then mated with HBV; Pten −/− mice to illustrate the role of hepatic tumor biomarker golgi membrane protein 73 (GP73)/ golgi membrane protein 1 (GOLM1) in hepatic oncogenesis. Results Pten deletion and HBV transgene synergistically aggravated liver injury, inflammation, fibrosis and development of mixed hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). GP73 was augmented in HBV; Pten −/− livers. Knockout of GP73 blunted the synergistic effect of deficient Pten and transgenic HBV on liver injury, inflammation, fibrosis and cancer development. Conclusions This mixed HCC-ICC mouse model mimics liver cancer patients harboring HBV infection and PTEN/AKT signaling pathway alteration. Targeting GP73 is a promising therapeutic strategy for cancer patients with HBV infection and PTEN alteration.

The annexins(ANX) family is widely present in the cell membrane, cytoplasm or extracellular matrix. As key tumor regulatory molecules, annexins A (ANX A) family can promote or inhibit invasion and metastasis of breast cancer cells by influencing cell membrane and cytoskeleton formation and participating in signaling pathways. ANX A family also plays a role in the apoptosis of breast cancer cells by regulation of pro-apoptotic proteins and cell cycle independent kinases (CDKs) and related pathways. In addition, ANX A family can also promote therapeutic resistance to a large number of drugs. For instance,ANX A1 enhances triple-negative breast cancer resistance by inducing epithelial-mesenchymal transformation. ANX A4 induces resistance by forming ANX A4-Fhit complexes and secretion of exosomes containing ANX A6 promotes paclitaxel resistance in breast cancer cells in a YAP1-dependent manner. So ANX A family may be a new target for breast cancer treatment.

Abstract Post-COVID-19 syndrome may be associated with the abnormal immune status. Compared with the unexposed age-matched elder group, PD-1 in the CD8+ T cells from recovered COVID-19 patients was significantly lower. IFN-γ in the plasma of COVID-19 convalescent patients was increased, which inhibited PD-1 expression in CD8+ T cells from COVID-19 convalescent patients. scRNA-seq bioinformatics analysis revealed that AKT/GSK3β may regulate the INF-γ/PD-1 axis in CD8+ T cells from COVID-19 convalescent patients. In parallel, an IFN-γ neutralizing antibody reduced AKT and increased GSK3β in PBMCs. An AKT agonist (SC79) significantly decreased p-GSK3β. Moreover, AKT decreased PD-1 on CD8+ T cells, and GSK3β increased PD-1 on CD8+ T cells according to flow cytometry analysis. Collectively, we demonstrated that recovered COVID-19 patients may develop long COVID. Increased IFN-γ in the plasma of recovered Wuhan COVID-19 patients contributed to PD-1 downregulation on CD8+ T cells by regulating the AKT/GSK3β signaling pathway.

Abstract The mood index $$r$$ r was used to describe evaluator attitudes regarding the progress of a project that formed the basis of a construction period prediction model. The degrees of pessimism $$\alpha$$ α and optimism $$\beta$$ β were introduced, and an analysis model was established using $$\alpha$$ α and $$\beta$$ β to predict the construction period and completion probability Firstly, the absolute construction period of each process of tunnel No. 2 can be obtained according to the measured daily average footage of each process of tunnel No. 1. Secondly, the probability of the stoppage caused by different factors can be obtained after the statistical analysis of the factors responsible for the stoppage of tunnel No. 1. Finally, the expected construction period and completion probability of tunnel No. 2 under different pessimism and optimism conditions are obtained by using the progress risk analysis theory of emotional models and the program evaluation and review technique method. An engineering application showed that the expected construction period increased, and the completion probability decreased considerably with increasing pessimism; the opposite trend occurred as optimism increased. During the process of risk management and control, the prediction model can be used to perform precise quantitative analysis of the expected construction period and completion probability, reduce the blindness of construction management, control decisions of complex giant tunnel projects, and provide a more accurate basis for decision makers to judge risks. The findings of this study can be applied to hydraulic tunnels and can provide a reference for traffic tunnels, railway tunnels, and other similar projects.

Abstract To explore the relationship between quantitative perfusion histogram parameters of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) with the expression of tumor tissue epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and EGFR gene mutations in non-small cell lung cancer (NSCLC). A total of 44 consecutive patients with known NSCLC were recruited from March 2018 to August 2021. Histogram parameters (mean, uniformity, skewness, energy, kurtosis, entropy, percentile) of each (Ktrans, Kep, Ve, Vp, Fp) were obtained by Omni Kinetics software. Immunohistochemistry staining was used in the detection of the expression of VEGF and EGFR protein, and the mutation of EGFR gene was detected by PCR. Corresponding statistical test was performed to compare the parameters and protein expression between squamous cell carcinoma (SCC) and adenocarcinoma (AC), as well as EGFR mutations and wild-type. Correlation analysis was used to evaluate the correlation between parameters with the expression of VEGF and EGFR protein. Fp (skewness, kurtosis, energy) were statistically significant between SCC and AC, and the area under the ROC curve were 0.733, 0.700 and 0.675, respectively. The expression of VEGF in AC was higher than in SCC. Fp (skewness, kurtosis, energy) were negatively correlated with VEGF (r = − 0.527, − 0.428, − 0.342); Ktrans (Q50) was positively correlated with VEGF (r = 0.32); Kep (energy), Ktrans (skewness, kurtosis) were positively correlated with EGFR (r = 0.622, r = 0.375, 0.358), some histogram parameters of Kep, Ktrans (uniformity, entropy) and Ve (kurtosis) were negatively correlated with EGFR (r = − 0.312 to − 0.644). Some perfusion histogram parameters were statistically significant between EGFR mutations and wild-type, they were higher in wild-type than mutated (P

Abstract Doxorubicin (DOX) is an effective anticancer drug with potent antitumour activity. However, the application of DOX is limited by its adverse reactions, such as depression. Taurine can alleviate depression induced by multiple factors. However, it is still unclear whether and how taurine improves DOX-induced depression. To address this question, the aim of this study was to explore the potential mechanism by which taurine protects against DOX-induced depression. Mice were randomly divided into three groups (n = 8): (1) the control group, (2) the DOX group, and (3) the DOX + taurine group. The open field test (OFT), elevated plus maze test, and forced swim test (FST) were first performed to assess the effects of DOX and taurine on the behaviour of mice. Next, a combined transcriptomic and metabolomic analysis was performed to analyse the possible antidepressive effect of taurine. Taurine pretreatment increased the total distance travelled and speed of mice in the OFT, increased the number of entries into the open arm and the time spent in the open arm, and reduced the immobility time in the FST. In addition, 179 differential genes and 51 differentially abundant metabolites were detected in the DOX + taurine group compared to the DOX group. Furthermore, differential genes and differentially abundant metabolites were found to be jointly involved in 21 pathways, which may be closely related to the antidepressant effect of taurine. Taurine alleviated DOX-induced depressive behaviour. The various pathways identified in this study, such as the serotonergic synapse and the inflammatory mediator regulation of TRP channels, may be key regulatory pathways related to depression and antidepressant effects.

Abstract Background The appropriateness of hypertension thresholds for triggering action to prevent cardiovascular and renal complications among non-White populations in the UK is subject to question. Our objective was to establish ethnicity-specific systolic blood pressure (SBP) cutoffs for ethnic minority populations and assess the efficacy of these ethnicity-specific cutoffs in predicting adverse outcomes. Methods We analyzed data from UK Biobank, which included 444,418 participants from White, South Asian, Black Caribbean, and Black African populations with no history of cardiorenal complications. We fitted Poisson regression models with continuous SBP and ethnic groups, using Whites as the referent category, for the composite outcome of atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease. We determined ethnicity-specific thresholds equivalent to the risks observed in Whites at SBP levels of 120, 130, and 140 mm Hg. We adjusted models for clinical characteristics, sociodemographic factors, and behavioral factors. The performance of ethnicity-specific thresholds for predicting adverse outcomes and associated population-attributable fraction (PAF) was assessed in ethnic minority groups. Results After a median follow-up of 12.5 years (interquartile range, 11.7–13.2), 32,662 (7.4%) participants had incident composite outcomes. At any given SBP, the predicted incidence rate of the composite outcome was the highest for South Asians, followed by White, Black Caribbean, and Black African. For an equivalent risk of outcomes observed in the White population at an SBP level of 140 mm Hg, the SBP threshold was lower for South Asians (123 mm Hg) and higher for Black Caribbean (156 mm Hg) and Black African (165 mm Hg). Furthermore, hypertension defined by ethnicity-specific thresholds was a stronger predictor and resulted in a larger PAF for composite outcomes in South Asians (21.5% [95% CI, 2.4,36.9] vs. 11.3% [95% CI, 2.6,19.1]) and Black Africans (7.1% [95% CI, 0.2,14.0] vs. 5.7 [95% CI, -16.2,23.5]) compared to hypertension defined by guideline-recommended thresholds. Conclusions Guideline-recommended blood pressure thresholds may overestimate risks for the Black population and underestimate risks for South Asians. Using ethnicity-specific SBP thresholds may improve risk estimation and optimize hypertension management toward the goal of eliminating ethnic disparities in cardiorenal complications.

Among persons born in China before 1980 and tested for vaccinia virus Tiantan strain (VVT), 28.7% (137/478) had neutralizing antibodies, 71.4% (25/35) had memory B-cell responses, and 65.7% (23/35) had memory T-cell responses to VVT. Because of cross-immunity between the viruses, these findings can help guide mpox vaccination strategies in China.

Objective To comprehensively explore the serological characteristics of anti-PP1Pk and potential therapeutic strategies for recurrent miscarriage in p-blood type pregnant women. Methods Neutralization with pigeon egg white and human plasma, disruption of IgM antibodies by 2-mercaptoethanol reagent, and complement adding were conducted. Anti-PP1Pk titers under different processing conditions, media and temperatures were determined, and neutralizing effect of human plasma on anti-PP1Pk and its sensitization complement ability were analyzed. Results The titers of anti-PP1Pk in saline and column agglutination were 4 and 8, respectively. Low temperature increased titers, while β-mercaptoethanol treatment significantly reduced them. Pigeon egg white partially neutralized anti-PP1Pk antibodies. Human plasma was also capable of reducing anti-PP1Pk titers with neutralization capability surpassing that of pigeon egg white, and there were individual differences in neutralization capability. Conclusion The anti-PP1Pk was a blend of antibodies encompassing both IgM and IgG types, exhibiting cold reactivity, and having the potential for complement activation. Human plasma emerges as an effective modulator for diminishing the efficacy of anti-PP1Pk. Plasma transfusion holds promise as a therapeutic avenue for addressing recurrent miscarriages in pregnant individuals with the p phenotype.