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Background: To assess the effect of pneumonia on the risk of mortality and other clinical outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD)., Methods: PubMed, EMBASE and Scopus were screened for observational cohort and case-control studies that reported outcomes in AECOPD patients with and without pneumonia. Pooled effect sizes were reported as relative risks (RR) or hazard ratio (HR) for categorical outcomes and as weighted mean difference (WMD) for continuous outcomes. The primary outcome was mortality. Secondary outcomes were risk of admission to intensive care unit (ICU), need for assisted ventilation and readmission as well as duration of stay at the hospital. The certainty of the evidence was assessed using the GRADE approach., Results: Thirteen studies were included. AECOPD patients with pneumonia had significantly higher risk of in-hospital mortality (RR 2.29, 95% CI: 1.40, 3.73), mortality at 1 month (RR 1.84, 95% CI: 1.09, 3.13), and 1 year or more of follow-up (HR 2.30, 95% CI: 1.15, 4.61) compared to AECOPD patients without pneumonia. Pneumonia was associated with significantly higher risk of admission to ICU (RR 2.79, 95% CI: 1.47, 5.28), need for assisted ventilation (RR 2.02, 95% CI: 1.52, 2.67), and longer hospital stay (in days) (WMD 3.31, 95% CI: 2.33, 4.29). The risk of readmission was comparable in the two groups of patients (RR 1.07, 95% CI: 0.97, 1.19). The overall quality of evidence for the outcomes was judged to be "Low"., Conclusion: Pneumonia during acute exacerbation of COPD may lead to increases in both short-term and long-term mortality as well as increased hospital stay, need for ventilatory support and admission to ICU. Our findings suggest the need for close monitoring, early intervention, and long-term follow-up, to improve the outcomes in AECOPD patients with concurrent pneumonia., (© 2024. The Author(s).)

Background: The mortality rate of COVID-19 patients with critical symptoms is reported to be 40.5%. Early identification of patients with poor progression in the critical cohort is essential to timely clinical intervention and reduction of mortality. Although older age, chronic diseases, have been recognized as risk factors for COVID-19 mortality, we still lack an accurate prediction method for every patient. This study aimed to delve into the cell-free DNA fragmentomics of critically ill patients, and develop new promising biomarkers for identifying the patients with high mortality risk., Methods: We utilized whole genome sequencing on the plasma cell-free DNA (cfDNA) from 33 COVID-19 patients with critical symptoms, whose outcomes were classified as survival (n = 16) and death (n = 17). Mitochondrial DNA (mtDNA) abundance and fragmentomic properties of cfDNA, including size profiles, ends motif and promoter coverages were interrogated and compared between survival and death groups., Results: Significantly decreased abundance (~ 76% reduction) and dramatically shorter fragment size of cell-free mtDNA were observed in deceased patients. Likewise, the deceased patients exhibited distinct end-motif patterns of cfDNA with an enhanced preference for "CC" started motifs, which are related to the activity of nuclease DNASE1L3. Several dysregulated genes involved in the COVID-19 progression-related pathways were further inferred from promoter coverages. These informative cfDNA features enabled a high PPV of 83.3% in predicting deceased patients in the critical cohort., Conclusion: The dysregulated biological processes observed in COVID-19 patients with fatal outcomes may contribute to abnormal release and modifications of plasma cfDNA. Our findings provided the feasibility of plasma cfDNA as a promising biomarker in the prognosis prediction in critically ill COVID-19 patients in clinical practice., (© 2024. The Author(s).)

Background: Malaria is a serious public health concern. Artemisinin and its derivatives are first-line drugs for the treatment of Plasmodium falciparum malaria. In mammals, artemisinin exhibits potent anti-inflammatory and immunoregulatory properties. However, it is unclear whether artemisinin plays a regulatory role in the innate immunity of mosquitoes, thereby affecting the development of Plasmodium in Anopheles when artemisinin and its metabolites enter mosquitoes. This study aims to determine the effect of dihydroartemisinin (DHA), a first-generation semisynthetic derivative of artemisinin, on innate immunity and malaria vector competence of Anopheles stephensi., Methods: Anopheles stephensi was fed Plasmodium-infected mice treated with DHA via gavage, Plasmodium-infected blood containing DHA in vitro, or DHA-containing sugar, followed by Plasmodium yoelii infection. The engorged female mosquitoes were separated and dissected 8 and 17 days after infection. Plasmodium oocysts and sporozoites were counted and compared between the control and DHA-treated groups. Additionally, total RNA and proteins were extracted from engorged mosquitoes 24 and 72 h post infection (hpi). Real-time polymerase chain reaction (PCR) and western blotting were performed to detect the transcriptional levels and protein expression of immune molecules in mosquitoes. Finally, the Toll signaling pathway was inhibited via RNA interference and the infection density was analyzed to confirm the role of the Toll signaling pathway in the effect of DHA on the vector competence of mosquitoes., Results: DHA treatment via different approaches significantly reduced the number of Plasmodium oocysts and sporozoites in mosquitoes. The transcriptional levels of anti-Plasmodium immune genes (including TEP1, LRIM1, and APL1C), Toll pathway genes (including Tube, MyD88, and Rel1), and the effector defensin 1 were upregulated by DHA treatment at 24 and 72 hpi. TEP1 and Rel1 protein expression was significantly induced under DHA treatment. However, Rel1 knockdown in DHA-treated mosquitoes abrogated DHA-mediated refractoriness to Plasmodium infection., Conclusions: DHA treatment effectively inhibited the development of P. yoelii in A. stephensi by upregulating mosquitoes' Toll signaling pathway, thereby influencing the susceptibility of Anopheles to Plasmodium., (© 2024. The Author(s).)

Background: X-linked intellectual disability-hypotonic facies syndrome-1 (MRXHF1) and Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome are caused by pathogenic variant in the ATRX gene, a member of the switch/sucrose non-fermentable (SWI-SNF) protein family that exhibits chromatin remodeling activity. These syndromes show a wide spectrum of clinical manifestations, such as distinctive dysmorphic features, mild-to-profound intellectual disability, motor development delay, seizures, urogenital abnormalities, and gastrointestinal disorders., Case Presentation and Literature Review: A 3-year-old boy from a Chinese non-consanguineous family was diagnosed with MRXHF1 by whole-exome sequencing. Comprehensive family history information was obtained. The Medline database was searched until 1st Aug 2023 for articles related to ATRX pathogenic variant. Data on gene/protein mutations and clinical symptoms were extracted. The proband showed intellectual disability, motor development delay, typical facial abnormalities, urogenital defect, behavior problems, and optical nerve dysplasia. A novel frameshift mutation c.399_400dup, (p.Leu134Cysfs*2) in the ATRX gene was the primary cause, which occurs right before the ATRXDNMT3-DNMT3L (ADD) domain of ATRX protein. Missense mutation is the most common variation type. The ADD and helicase-like domains are the most frequently affected domains. Epilepsy, congenital heart disease, urogenital defect, acoustic defect, and optical defect are more prevalent in patients with frameshift mutations compared to those with missense mutations. There are more urogenital defects with C-terminal frameshift mutations than with N-terminal frameshift mutations., Conclusion: We described a novel frameshift mutation in the ATRX gene in a patient with MRXHF1 syndrome and summarized the genotype-phenotype relationship of ATRX pathogenic variant by variation type and affected protein domain. The regulatory mechanism underlying ATRX variant requires comprehensive analysis in future studies., (© 2024. The Author(s).)

Background: Xuefu Zhuyu decoction (XFZYD) has been extensively utilized to treat traumatic brain injury (TBI). However, the bioactive compounds and the underlying mechanisms have not yet been elucidated., Objectives: This study aimed to investigate the bioactive constituents of XFYZD that are absorbed in the blood and the mechanisms in treating TBI., Methods: The study presents an integrated strategy in three steps to investigate the material basis and pharmacological mechanisms of XFZYD. The first step involves: (1) performing metabolomics analysis of XFZYD to obtain the main functions and targets; (2) screening the blood-entry ingredients and targets of XFZYD from databases; (3) obtaining the potential components targeting the key functions by integrated analysis of metabolomics and network pharmacology. The second step involves screening pharmacological effects with active ingredients in vitro. In the third step, the effects of the top active compound were validated in vivo, and the mechanisms were explored by protein antagonist experiments., Results: Metabolomics analysis revealed that XFZYD treated TBI mice mainly through affecting the functions of blood vessels. We screened 62 blood-entry ingredients of XFZYD by network pharmacology. Then, we focused on 39 blood-entry ingredients related to vascular genes enriched by XFZYD-responsive metabolites. Performing the natural products library, we verified that hydroxysafflor yellow A (HSYA), vanillin, ligustilide, paeoniflorin, and other substances promoted endothelial cell proliferation significantly compared to the control group. Among them, the efficacy of HSYA was superior. Further animal studies demonstrated that HSYA treatment alleviated neurological dysfunction in TBI mice by mNSS and foot fault test, and decreased neuronal damage by HE, nissl, and TUNEL staining. HSYA increased the density of cerebral microvessels, raised the expression of angiogenesis marker proteins VEGFA and CD34, and activated the PI3K/Akt/mTOR signaling pathway significantly. The angiogenic effects disappeared after the intervention of PI3K antagonist LY294002., Conclusion: By applying a novel strategy of integrating network pharmacology of constituents absorbed in blood with metabolomics, the research screened HSYA as one of the top bioactive constituents of XFZYD, which stimulates angiogenesis by activating the PI3K/Akt/mTOR signaling pathway after TBI., (© 2024. The Author(s).)

Background: Postoperative cognitive dysfunction (POCD) is common following surgery in elderly patients. The role of the preoperative gut microbiota in POCD has attracted increasing attention, but the potential underlying mechanisms remain unclear. This research aimed to investigate the impact of the preoperative gut microbiota on POCD., Methods: Herein, we analyzed the preoperative gut microbiota of POCD patients through a prospective specimen collection and retrospective blinded evaluation study. Then, we transferred the preoperative gut microbiota of POCD patients to antibiotic-treated rats and established POCD model by abdominal surgery to explore the impact of the preoperative gut microbiota on pre- and postoperative cognitive function and systemic inflammation. The gut microbiota was analyzed using 16S rRNA sequencing analysis. The Morris water maze test was performed to evaluate learning and memory abilities. The inflammatory cytokines TNF-α, IL-1β and IL-6 in the serum and hippocampus were measured by ELISA. Microglia were examined by immunofluorescence staining for Iba-1., Results: Based on the decrease in the postoperative MMSE score, 24 patients were identified as having POCD and were matched with 24 control patients. Compared with control patients, POCD patients exhibited higher BMI and lower preoperative MMSE score. The preoperative gut microbiota of POCD patients had lower bacterial richness but a larger distribution, decreased abundance of Firmicutes and increased abundance of Proteobacteria than did that of control patients. Compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients presented an increased abundance of Desulfobacterota, decreased cognitive function, increased levels of TNF-α and IL-1β in the serum, increased levels of TNF-α and greater microglial activation in the hippocampus. Additionally, correlation analysis revealed a positive association between the abundance of Desulfobacterota and the level of serum TNF-α in rats. Then, we performed abdominal surgery to investigate the impact of the preoperative gut microbiota on postoperative conditions, and the surgery did indeed cause POCD and inflammatory response. Notably, compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients displayed exacerbated cognitive impairment; increased levels of TNF-α, IL-1β and IL-6 in the serum and hippocampus; and increased activation of microglia in the hippocampus., Conclusions: Our findings suggest that the preoperative gut microbiota of POCD patients can induce preoperative and aggravate postoperative cognitive impairment and systemic inflammation in rats. Modulating inflammation by targeting the gut microbiota might be a promising approach for preventing POCD., (© 2024. The Author(s).)

Background: The coexistence of cardiovascular disease and chronic kidney disease, termed chronic cardiovascular-kidney disorder (CCV-KD), is increasingly prevalent. However, limited studies have assessed the association between cardiovascular health (CVH), assessed by the American Heart Association's Life's Essential 8 (LE8), and CCV-KD., Methods: We conducted a prospective cohort study using data from UK Biobank. Participants without cardiovascular disease and chronic kidney disease at baseline and having complete data on metrics of LE8 were included (N = 125,986). LE8 included eight metrics, and the aggregate score was categorized as low (< 50 points), intermediate (50 to < 80 points), and high (≥ 80 points), with a higher score indicating better CVH health. Adjusted Cox proportional hazard models were conducted to explore the association of CVH with the risk of CCV-KD. The adjusted proportion of population attributable risk (PAR%) was used to calculate the population-level risk caused by low or intermediate CVH., Results: During a median follow-up of 12.5 years, 1,054 participants (0.8%) had incident CCV-KD. Participants with intermediate and high CVH had 54% (HR = 0.46, 95% CI: 0.40-0.54, P < 0.001) and 75% (HR = 0.25, 95% CI: 0.18-0.34, P < 0.001) lower risks of incident CCV-KD compared with those in low CVH group. There was an approximately dose-response linear relationship between the overall LE8 score and incident CCV-KD. The risk of incident CCV-KD decreased by 30% (HR = 0.70, 95% CI: 0.67-0.74, P < 0.001) for a 10-point increment of LE8 score. The adjusted PAR% of lower overall CVH was 47.4% (95% CI: 31.6%-59.8%)., Conclusions: Better CVH, assessed by using LE8 score, was strongly associated with decreased risk of incident CCV-KD. These findings imply optimizing CVH may be a preventive strategy to reduce the burden of CCV-KD., (© 2024. The Author(s).)

Background: An elevated endogenous cortisol level due to the peripartum stress is one of the risk factors of postpartum bovine uterine infections. Selenium is a trace element that elicits anti-inflammation and antioxidation properties. This study aimed to reveal the modulatory effect of selenium on the inflammatory response of primary bovine endometrial stromal cells in the presence of high-level cortisol. The cells were subjected to lipopolysaccharide to establish cellular inflammation. The mRNA expression of toll-like receptor 4 (TLR4), proinflammatory factors, and selenoproteins was measured with qPCR. The activation of NF-κB and MAPK signalling pathways was detected with Western blot and immunofluorescence., Results: The pretreatment with sodium selenite (2 and 4 µΜ) resulted in a down-regulation of TLR4 and genes encoding proinflammatory factors, including interleukin (IL)-1β, IL-6, IL-8, tumour necrosis factor α, cyclooxygenase 2, and inducible nitric oxide synthase. Selenium inhibited the activation of NF-κB and the phosphorylation of mitogen-activated protein kinase kinase, extracellular signal-regulated kinase, p38MAPK and c-Jun N-terminal kinase/stress-activated protein kinase. The suppression of those genes and pathways by selenium was more significant in the presence of high cortisol level (30 ng/mL). Meanwhile the gene expression of glutathione peroxidase 1 and 4 was promoted by selenium, and was even higher in the presence of cortisol and selenium., Conclusions: The anti-inflammatory action of selenium is probably mediated through NF-κB and MAPK, and is augmented by cortisol in primary bovine endometrial stromal cells., (© 2024. The Author(s).)

Background: The predictive value of systemic inflammatory response index (SIRI) for stroke-associated pneumonia (SAP) risk in patients with acute ischemic stroke (AIS) treated by thrombectomy remains unclear. This study aimed to investigate the predictive value of SIRI for SAP in patients with AIS treated by thrombectomy., Methods: We included AIS patients treated by thrombectomy between August 2018 and August 2022 at our institute. We used multivariate logistic regression to construct the prediction model and performed a receiver operating characteristic curve analysis to evaluate the ability of SIRI to predict SAP and constructed a calibration curve to evaluate the prediction accuracy of the model. We evaluated the clinical application value of the nomogram using decision curve analysis., Results: We included 84 eligible patients with AIS in the analysis, among which 56 (66.7%) had SAP. In the univariate analysis, there were significant differences in sex (p = 0.035), National Institute of Health Stroke Scale score at admission ≥ 20 (p = 0.019) and SIRI (p < 0.001). The results of multivariable logistic analysis showed that the risk of SAP increased with the SIRI value (OR = 1.169, 95% CI = 1.049-1.344, p = 0.014). Age ≥ 60 (OR = 4.076, 95% CI = 1.251-14.841, p = 0.024) was also statistically significant. A nomogram with SIRI showed good prediction accuracy for SAP in AIS patients treated by thrombectomy (C-index value = 0.774)., Conclusions: SIRI is an independent predictor for SAP in patients with AIS treated by thrombectomy. A high SIRI value may allow for the early identification of patients with AIS treated by thrombectomy at high risk for SAP., (© 2024. The Author(s).)

Purpose: Bladder cancer (BLCA) is a prevalent malignancy. Dysregulated propionate metabolism, a key cancer factor, suggests a potential target for treating metastatic cancer. However, a complete understanding of the link between propionate metabolism-related genes (PMRGs) and bladder cancer is lacking., Methods: From the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we gathered BLCA patient data, which was classified into distinct subgroups using non-negative matrix factorization (NMF). Survival and pathway analyses were conducted between these clusters. The PMRGs model, created through univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses, was assessed for prognostic significance using Kaplan-Meier and receiver operating characteristic (ROC) curves. A comprehensive evaluation included clinical, tumor microenvironment (TME), drug sensitivity, and immunotherapy analyses. Finally, the expression of HSD17B1 essential genes was confirmed via quantitative real-time polymerase chain reaction (qRT-PCR), with further validation through Transwell, wound healing, colony-formation, and EDU assays., Results: We discovered two distinct subcategories (CA and CB) within BLCA using NMF analysis, with CA demonstrating significantly better overall survival compared to CB. Additionally, six PMRGs emerged as critical factors associated with propionate metabolism and prognosis. Kaplan-Meier analysis revealed that high-risk PMRGs were correlated with a poorer prognosis in BLCA patients. Moreover, significant differences were observed between the two groups in terms of infiltrated immune cells, immune checkpoint expression, TME scores, and drug sensitivity. Notably, we found that suppressing HSD17B1 gene expression inhibited the invasion of bladder cancer cells., Conclusion: Our study proposes molecular subtypes and a PMRG-based score as promising prognostic indicators in BLCA. Additionally, cellular experiments underscore the pivotal role of HSD17B1 in bladder cancer metastasis and invasion, suggesting its potential as a novel therapeutic target., (© 2024. The Author(s).)

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. NAFLD leads to liver fibrosis and hepatocellular carcinoma, and it also has systemic effects associated with metabolic diseases, cardiovascular diseases, chronic kidney disease, and malignant tumors. Therefore, it is important to diagnose NAFLD early to prevent these adverse effects., Methods: The GSE89632 dataset was downloaded from the Gene Expression Omnibus database, and then the optimal genes were screened from the data cohort using lasso and Support Vector Machine Recursive Feature Elimination (SVM-RFE). The ROC values of the optimal genes for the diagnosis of NAFLD were calculated. The relationship between optimal genes and immune cells was determined using the DECONVOLUTION algorithm CIBERSORT. Finally, the specificity and sensitivity of the diagnostic genes were verified by detecting the expression of the diagnostic genes in blood samples from 320 NAFLD patients and liver samples from 12 mice., Results: Through machine learning we identified FOSB, GPAT3, RGCC and RNF43 were the key diagnostic genes for NAFLD, and they were further demonstrated by a receiver operating characteristic curve analysis. We found that the combined diagnosis of the four genes identified NAFLD samples well from normal samples (AUC = 0.997). FOSB, GPAT3, RGCC and RNF43 were strongly associated with immune cell infiltration. We also experimentally examined the expression of these genes in NAFLD patients and NAFLD mice, and the results showed that these genes are highly specific and sensitive., Conclusions: Data from both clinical and animal studies demonstrate the high sensitivity, specificity and safety of FOSB, GPAT3, RGCC and RNF43 for the diagnosis of NAFLD. The relationship between diagnostic key genes and immune cell infiltration may help to understand the development of NAFLD. The study was reviewed and approved by Ethics Committee of Tianjin Second People's Hospital in 2021 (ChiCTR1900024415)., (© 2024. The Author(s).)

Background: Waardenburg syndrome (WS) is a rare genetic disorder mainly characterized by hearing loss and pigmentary abnormalities. Currently, seven causative genes have been identified for WS, but clinical genetic testing results show that 38.9% of WS patients remain molecularly unexplained. In this study, we performed multi-data integration analysis through protein-protein interaction and phenotype-similarity to comprehensively decipher the potential causative factors of undiagnosed WS. In addition, we explored the association between genotypes and phenotypes in WS with the manually collected 443 cases from published literature., Results: We predicted two possible WS pathogenic genes (KIT, CHD7) through multi-data integration analysis, which were further supported by gene expression profiles in single cells and phenotypes in gene knockout mouse. We also predicted twenty, seven, and five potential WS pathogenic variations in gene PAX3, MITF, and SOX10, respectively. Genotype-phenotype association analysis showed that white forelock and telecanthus were dominantly present in patients with PAX3 variants; skin freckles and premature graying of hair were more frequently observed in cases with MITF variants; while aganglionic megacolon and constipation occurred more often in those with SOX10 variants. Patients with variations of PAX3 and MITF were more likely to have synophrys and broad nasal root. Iris pigmentary abnormality was more common in patients with variations of PAX3 and SOX10. Moreover, we found that patients with variants of SOX10 had a higher risk of suffering from auditory system diseases and nervous system diseases, which were closely associated with the high expression abundance of SOX10 in ear tissues and brain tissues., Conclusions: Our study provides new insights into the potential causative factors of WS and an alternative way to explore clinically undiagnosed cases, which will promote clinical diagnosis and genetic counseling. However, the two potential disease-causing genes (KIT, CHD7) and 32 potential pathogenic variants (PAX3: 20, MITF: 7, SOX10: 5) predicted by multi-data integration in this study are all computational predictions and need to be further verified through experiments in follow-up research., (© 2024. The Author(s).)

Objective: To develop a nomogram based on tumor and peritumoral edema (PE) radiomics features extracted from preoperative multiparameter MRI for predicting brain invasion (BI) in atypical meningioma (AM)., Methods: In this retrospective study, according to the 2021 WHO classification criteria, a total of 469 patients with pathologically confirmed AM from three medical centres were enrolled and divided into training (n = 273), internal validation (n = 117) and external validation (n = 79) cohorts. BI was diagnosed based on the histopathological examination. Preoperative contrast-enhanced T1-weighted MR images (T1C) and T2-weighted MR images (T2) for extracting meningioma features and T2-fluid attenuated inversion recovery (FLAIR) sequences for extracting meningioma and PE features were obtained. The multiple logistic regression was applied to develop separate multiparameter radiomics models for comparison. A nomogram was developed by combining radiomics features and clinical risk factors, and the clinical usefulness of the nomogram was verified using decision curve analysis., Results: Among the clinical factors, PE volume and PE/tumor volume ratio are the risk of BI in AM. The combined nomogram based on multiparameter MRI radiomics features of meningioma and PE and clinical indicators achieved the best performance in predicting BI in AM, with area under the curve values of 0.862 (95% CI, 0.819-0.905) in the training cohort, 0.834 (95% CI, 0.780-0.908) in the internal validation cohort and 0.867 (95% CI, 0.785-0.950) in the external validation cohort, respectively., Conclusions: The nomogram based on tumor and PE radiomics features extracted from preoperative multiparameter MRI and clinical factors can predict the risk of BI in patients with AM., (© 2024. The Author(s).)

BACKGROUND ACMELLA RADICANS: (Jacquin) R.K. Jansen is a new invasive species record for Yunnan Province, China. Native to Central America, it has also been recently recorded invading other parts of Asia. To prevent this weed from becoming a serious issue, an assessment of its ecological impacts and potential distribution is needed. We predicted the potential distribution of A. radicans in China using the MaxEnt model and its ecological impacts on local plant communities and soil nutrients were explored. RESULTS: Simulated training using model parameters produced an area under curve value of 0.974, providing a high degree of confidence in model predictions. Environmental variables with the greatest predictive power were precipitation of wettest month, isothermality, topsoil TEB (total exchangeable bases), and precipitation seasonality, with a cumulative contribution of more than 72.70% and a cumulative permutation importance of more than 69.20%. The predicted potential suitable area of A. radicans in China is concentrated in the southern region. Projected areas of A. radicans ranked as high and moderately suitable comprised 5425 and 26,338 km 2 , accounting for 0.06 and 0.27% of the Chinese mainland area, respectively. Over the 5 years of monitoring, the population density of A. radicans increased while at the same time the population density and importance values of most other plant species declined markedly. Community species richness, diversity, and evenness values significantly declined. Soil organic matter, total N, total P, available N, and available P concentrations decreased significantly with increasing plant cover of A. radicans, whereas pH, total K and available K increased. CONCLUSION: Our study was the first to show that A. radicans is predicted to expand its range in China and may profoundly affect plant communities, species diversity, and the soil environment. Early warning and monitoring of A. radicans must be pursued with greater vigilance in southern China to prevent its further spread., (© 2024. The Author(s).)

Background: An isokinetic moment curve (IMC) pattern-damaged structure prediction model may be of considerable value in assisting the diagnosis of knee injuries in clinical scenarios. This study aimed to explore the association between irregular IMC patterns and specific structural damages in the knee, including anterior cruciate ligament (ACL) rupture, meniscus (MS) injury, and patellofemoral joint (PFJ) lesions, and to develop an IMC pattern-damaged structure prediction model., Methods: A total of 94 subjects were enrolled in this study and underwent isokinetic testing of the knee joint (5 consecutive flexion-extension movements within the range of motion of 90°-10°, 60°/s). Qualitative analysis of the IMCs for all subjects was completed by two blinded examiners. A multinomial logistic regression analysis was used to investigate whether a specific abnormal curve pattern was associated with specific knee structural injuries and to test the predictive effectiveness of IMC patterns for specific structural damage in the knee., Results: The results of the multinomial logistic regression revealed a significant association between the irregular IMC patterns of the knee extensors and specific structural damages ("Valley" - ACL, PFJ, and ACL + MS, "Drop" - ACL, and ACL + MS, "Shaking" - ACL, MS, PFJ, and ACL + MS). The accuracy and Macro-averaged F1 score of the predicting model were 56.1% and 0.426, respectively., Conclusion: The associations between irregular IMC patterns and specific knee structural injuries were identified. However, the accuracy and Macro-averaged F 1 score of the established predictive model indicated its relatively low predictive efficacy. For the development of a more accurate predictive model, it may be essential to incorporate angle-specific and/or speed-specific analyses of qualitative and quantitative data in isokinetic testing. Furthermore, the utilization of artificial intelligence image recognition technology may prove beneficial for analyzing large datasets in the future., (© 2024. The Author(s).)

Biomedical terminologies play a vital role in managing biomedical data. Missing IS-A relations in a biomedical terminology could be detrimental to its downstream usages. In this paper, we investigate an approach combining logical definitions and lexical features to discover missing IS-A relations in two biomedical terminologies: SNOMED CT and the National Cancer Institute (NCI) thesaurus. The method is applied to unrelated concept-pairs within non-lattice subgraphs: graph fragments within a terminology likely to contain various inconsistencies. Our approach first compares whether the logical definition of a concept is more general than  that of the other concept. Then, we check whether the lexical features of the concept are contained in those of the other concept. If both constraints are satisfied, we suggest a potentially missing IS-A relation between the two concepts. The method identified 982 potential missing IS-A relations for SNOMED CT and 100 for NCI thesaurus. In order to assess the efficacy of our approach, a random sample of results belonging to the "Clinical Findings" and "Procedure" subhierarchies of SNOMED CT and results belonging to the "Drug, Food, Chemical or Biomedical Material" subhierarchy of the NCI thesaurus were evaluated by domain experts. The evaluation results revealed that 118 out of 150 suggestions are valid for SNOMED CT and 17 out of 20 are valid for NCI thesaurus., (© 2024. The Author(s).)

Background: COVID-19 has been shown to increase the risk of extracorporeal coagulation during hemodialysis in patients, but the underlying mechanism remains unclear. This study aimed to investigate the effect and mechanism of COVID-19 on the risk of extracorporeal coagulation in patients with chronic kidney disease undergoing hemodialysis., Methods: A retrospective analysis of the extracorporeal coagulation status of 339 hemodialysis patients at our center before and after COVID-19 infection was performed, including subgroup analyses. Post-infection blood composition was analyzed by protein spectrometry and ELISA., Results: Compared to the pre-COVID-19 infection period, COVID-19-induced extracorporeal coagulation predominantly occurred in patients with severe/critical symptoms. Further proteomic analysis demonstrated that in patients with severe/critical symptoms, the coagulation cascade reaction, platelet activation, inflammation, and oxidative stress-related pathways were significantly amplified compared to those in patients with no/mild symptoms. Notably, the vWF/FBLN5 pathway, which is associated with inflammation, vascular injury, and coagulation, was significantly upregulated., Conclusions: Patients with severe/critical COVID-19 symptoms are at a higher risk of extracorporeal coagulation during hemodialysis, which is associated with the upregulation of the vWF/FBLN5 signaling pathway. These findings highlight the importance of early anticoagulant therapy initiation in COVID-19 patients with severe/critical symptoms, particularly those undergoing hemodialysis. Additionally, vWF/FBLN5 upregulation may be a novel mechanism for virus-associated thrombosis/coagulation., (© 2024. The Author(s).)

Background: Alzheimer's Disease (AD) is a devastating disease that destroys memory and other cognitive functions. There has been an increasing research effort to prevent and treat AD. In the US, two major data sharing resources for AD research are the National Alzheimer's Coordinating Center (NACC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI); Additionally, the National Institutes of Health (NIH) Common Data Elements (CDE) Repository has been developed to facilitate data sharing and improve the interoperability among data sets in various disease research areas., Method: To better understand how AD-related data elements in these resources are interoperable with each other, we leverage different representation models to map data elements from different resources: NACC to ADNI, NACC to NIH CDE, and ADNI to NIH CDE. We explore bag-of-words based and word embeddings based models (Word2Vec and BioWordVec) to perform the data element mappings in these resources., Results: The data dictionaries downloaded on November 23, 2021 contain 1,195 data elements in NACC, 13,918 in ADNI, and 27,213 in NIH CDE Repository. Data element preprocessing reduced the numbers of NACC and ADNI data elements for mapping to 1,099 and 7,584 respectively. Manual evaluation of the mapping results showed that the bag-of-words based approach achieved the best precision, while the BioWordVec based approach attained the best recall. In total, the three approaches mapped 175 out of 1,099 (15.92%) NACC data elements to ADNI; 107 out of 1,099 (9.74%) NACC data elements to NIH CDE; and 171 out of 7,584 (2.25%) ADNI data elements to NIH CDE., Conclusions: The bag-of-words based and word embeddings based approaches showed promise in mapping AD-related data elements between different resources. Although the mapping approaches need further improvement, our result indicates that there is a critical need to standardize CDEs across these valuable AD research resources in order to maximize the discoveries regarding AD pathophysiology, diagnosis, and treatment that can be gleaned from them., (© 2024. The Author(s).)

Endosomal single-stranded RNA-sensing Toll-like receptor-7/8 (TLR7/8) plays a pivotal role in inflammation and immune responses and autoimmune diseases. However, the mechanisms underlying the initiation of the TLR7/8-mediated autoimmune signaling remain to be fully elucidated. Here, we demonstrate that miR-574-5p is aberrantly upregulated in tissues of lupus prone mice and in the plasma of lupus patients, with its expression levels correlating with the disease activity. miR-574-5p binds to and activates human hTLR8 or its murine ortholog mTlr7 to elicit a series of MyD88-dependent immune and inflammatory responses. These responses include the overproduction of cytokines and interferons, the activation of STAT1 signaling and B lymphocytes, and the production of autoantigens. In a transgenic mouse model, the induction of miR-574-5p overexpression is associated with increased secretion of antinuclear and anti-dsDNA antibodies, increased IgG and C3 deposit in the kidney, elevated expression of inflammatory genes in the spleen. In lupus-prone mice, lentivirus-mediated silencing of miR-574-5p significantly ameliorates major symptoms associated with lupus and lupus nephritis. Collectively, these results suggest that the miR-574-5p-hTLR8/mTlr7 signaling is an important axis of immune and inflammatory responses, contributing significantly to the development of lupus and lupus nephritis., (© 2024. The Author(s).)

Background: Fecal impaction is a digestive system disease, that is most common in the elderly population and becomes more prevalent with increasing age. Manual removal can successfully remove the impaction in 80% of fecal impaction cases. In severe cases, endoscopy and surgery may be necessary., Case Presentation: A 78-year-old Han Chinese man living in a nursing home was diagnosed with fecal impaction; his initial symptom was overflow diarrhea, which is a rare occurrence with regard to fecal impaction. Nevertheless, we were able to effectively treat this situation by employing a new medical device that presents a novel method for addressing fecal impaction., Conclusion: Early identification of fecal impaction with atypical symptoms is crucial to provide proper emergency management. A safe and noninvasive treatment method, especially for elderly patients with fecal impaction, should be chosen., (© 2024. The Author(s).)

Background: For patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD), effective second-line regimens are urgently needed. Mesenchymal stromal cells (MSCs) have been used as salvage regimens for SR-aGVHD in the past. However, clinical trials and an overall understanding of the molecular mechanisms of MSCs combined with basiliximab for SR-aGVHD are limited, especially in haploidentical haemopoietic stem cell transplantation (HID HSCT)., Methods: The primary endpoint of this multicentre, randomized, controlled trial was the 4-week complete response (CR) rate of SR-aGVHD. A total of 130 patients with SR-aGVHD were assigned in a 1:1 randomization schedule to the MSC group (receiving basiliximab plus MSCs) or control group (receiving basiliximab alone) (NCT04738981)., Results: Most enrolled patients (96.2%) received HID HSCT. The 4-week CR rate of SR-aGVHD in the MSC group was obviously better than that in the control group (83.1% vs. 55.4%, P = 0.001). However, for the overall response rates at week 4, the two groups were comparable. More patients in the control group used ≥ 6 doses of basiliximab (4.6% vs. 20%, P = 0.008). We collected blood samples from 19 consecutive patients and evaluated MSC-derived immunosuppressive cytokines, including HO1, GAL1, GAL9, TNFIA6, PGE2, PDL1, TGF-β and HGF. Compared to the levels before MSC infusion, the HO1 (P = 0.0072) and TGF-β (P = 0.0243) levels increased significantly 1 day after MSC infusion. At 7 days after MSC infusion, the levels of HO1, GAL1, TNFIA6 and TGF-β tended to increase; however, the differences were not statistically significant. Although the 52-week cumulative incidence of cGVHD in the MSC group was comparable to that in the control group, fewer patients in the MSC group developed cGVHD involving ≥3 organs (14.3% vs. 43.6%, P = 0.006). MSCs were well tolerated, no infusion-related adverse events (AEs) occurred and other AEs were also comparable between the two groups. However, patients with malignant haematological diseases in the MSC group had a higher 52-week disease-free survival rate than those in the control group (84.8% vs. 65.9%, P = 0.031)., Conclusions: For SR-aGVHD after allo-HSCT, especially HID HSCT, the combination of MSCs and basiliximab as the second-line therapy led to significantly better 4-week CR rates than basiliximab alone. The addition of MSCs not only did not increase toxicity but also provided a survival benefit., (© 2024. The Author(s).)

Objective: The primary object of this study is to analyze chromosomal abnormalities in miscarriages detected by copy number variants sequencing (CNV-Seq), establish potential pathways or genes related to miscarriages, and provide guidance for birth health in the following pregnancies., Methods: This study enrolled 580 miscarriage cases with paired clinical information and chromosomal detection results analyzed by CNV-Seq. Further bioinformatic analyses were performed on validated pathogenic CNVs (pCNVs)., Results: Of 580 miscarriage cases, three were excluded as maternal cell contamination, 357 cases showed abnormal chromosomal results, and the remaining 220 were normal, with a positive detection rate of 61.87% (357/577). In the 357 miscarriage cases, 470 variants were discovered, of which 65.32% (307/470) were pathogenic. Among all variants detected, 251 were numerical chromosomal abnormalities, and 219 were structural abnormalities. With advanced maternal age, the proportion of numerical abnormalities increased, but the proportion of structural abnormalities decreased. Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis revealed that eleven pathways and 636 biological processes were enriched in pCNVs region genes. Protein-protein interaction analysis of 226 dosage-sensitive genes showed that TP53, CTNNB1, UBE3A, EP300, SOX2, ATM, and MECP2 might be significant in the development of miscarriages., Conclusion: Our study provides evidence that chromosomal abnormalities contribute to miscarriages, and emphasizes the significance of microdeletions or duplications in causing miscarriages apart from numerical abnormalities. Essential genes found in pCNVs regions may account for miscarriages which need further validation., (© 2024. The Author(s).)

Background: As the demand and application of engineered nanomaterials have increased, their potential toxicity to the central nervous system has drawn increasing attention. Tunneling nanotubes (TNTs) are novel cell-cell communication that plays a crucial role in pathology and physiology. However, the relationship between TNTs and nanomaterials neurotoxicity remains unclear. Here, three types of commonly used engineered nanomaterials, namely cobalt nanoparticles (CoNPs), titanium dioxide nanoparticles (TiO 2 NPs), and multi-walled carbon nanotubes (MWCNTs), were selected to address this limitation., Results: After the complete characterization of the nanomaterials, the induction of TNTs formation with all of the nanomaterials was observed using high-content screening system and confocal microscopy in both primary astrocytes and U251 cells. It was further revealed that TNT formation protected against nanomaterial-induced neurotoxicity due to cell apoptosis and disrupted ATP production. We then determined the mechanism underlying the protective role of TNTs. Since oxidative stress is a common mechanism in nanotoxicity, we first observed a significant increase in total and mitochondrial reactive oxygen species (namely ROS, mtROS), causing mitochondrial damage. Moreover, pretreatment of U251 cells with either the ROS scavenger N-acetylcysteine or the mtROS scavenger mitoquinone attenuated nanomaterial-induced neurotoxicity and TNTs generation, suggesting a central role of ROS in nanomaterials-induced TNTs formation. Furthermore, a vigorous downstream pathway of ROS, the PI3K/AKT/mTOR pathway, was found to be actively involved in nanomaterials-promoted TNTs development, which was abolished by LY294002, Perifosine and Rapamycin, inhibitors of PI3K, AKT, and mTOR, respectively. Finally, western blot analysis demonstrated that ROS and mtROS scavengers suppressed the PI3K/AKT/mTOR pathway, which abrogated TNTs formation., Conclusion: Despite their biophysical properties, various types of nanomaterials promote TNTs formation and mitochondrial transfer, preventing cell apoptosis and disrupting ATP production induced by nanomaterials. ROS/mtROS and the activation of the downstream PI3K/AKT/mTOR pathway are common mechanisms to regulate TNTs formation and mitochondrial transfer. Our study reveals that engineered nanomaterials share the same molecular mechanism of TNTs formation and intercellular mitochondrial transfer, and the proposed adverse outcome pathway contributes to a better understanding of the intercellular protection mechanism against nanomaterials-induced neurotoxicity., (© 2024. The Author(s).)

Wu-tou decoction (WTD), a traditional Chinese medicine prescription, is used to treat rheumatoid arthritis (RA). It works by controlling intestinal flora and its metabolites, which in turn modulates the inflammatory response and intestinal barrier function. Small molecular compounds (SM) and polysaccharides (PS) were the primary constituents of WTD extract. In this work, a model of adjuvant-induced arthritis (AIA) in rats was established and treated with WTD, SM, and PS, respectively. 16S rRNA gene sequencing was used to examine the regulatory impact of the various groups on the disturbance of the gut flora induced by RA. Further, since PS cannot be absorbed into the blood, the influence of PS on the absorption and metabolism of SM was studied by examining their pharmacokinetic (PK) parameters of 23 active components in SM by UPLC-MS/MS. WTD was found to be more effective than PS and SM in alleviating arthritis in AIA rats, which may be related to changes in gut flora. The PK properties of 13 active compounds were altered after PS intervene. Based on the findings, PS may be able to manage the disruption of intestinal microbiota, enhance the intestinal environment of model animals, and hence influence SM absorption and metabolism., (© 2024. The Author(s).)

Background: The evidence of preferences for infection prevention and control (IPC) intervention from system perspective was lacked. This study aimed to elicit nurses' preferences for the intervention designed to improve IPC behaviors based on the Systems Engineering Initiative to Patient Safety (SEIPS) model using Discrete Choice Experiment (DCE)., Methods: A DCE was conducted among nurses who were on active duty and willing to participate from July 5th to 10th, 2021 in a tertiary hospital in Ganzhou City, Jiangxi Province, using convenience sampling. A self-administered questionnaire included scenarios formed by six attributes with varying levels based on SEIPS model: person, organization, tools and technology, tasks, internal environment and external environment. A conditional logit and latent class logit model were performed to analyze the data., Results: A total of 257 valid questionnaires were analyzed among nurses. The results from the latent class logit model show that nurses' preferences can be divided into three classes. For nurses in multifaceted-aspect-preferred class (41.9%), positive coefficients were obtained in those six attributes. For person-preferred class (19.7%), only person was positively significant. For environment-preferred class (36.4%), the most important attribute were tasks, tools and technology, internal environment and external environment., Conclusions: This finding suggest that nurses have three latent-class preferences for interventions. Multifaceted interventions to improve IPC behaviors based on the SEIPS model are preferred by most nurses. Moreover, relevant measured should be performed targeted the latent class of person-preferred and external-environment-preferred nurses., (© 2024. The Author(s).)

Background: Markers that can be used to evaluate the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) remain undefined., Objective: This study aimed to investigate the prognostic impact of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in patients with HNSCC who underwent surgery-based treatment for the first time., Methods: This retrospective study included patients HNSCC who underwent surgery-based treatment at our institution between January 2018 and December 2020. Specificity and sensitivity were analyzed using receiver operating characteristic (ROC) curves and the critical value was determined. Patients were divided into low and high groups according to NLR, PLR, and LMR the critical value. Log-rank and Cox proportional hazards models were used to evaluate the associations between preoperative NLR, PLR, LMR, and overall survival (OS)., Results: A total of 304 patients with HNSCC were included, of whom 190 (62.5%) and 114 (37.5%), 203 (66.8%) and 101 (33.2%), 98 (32.2%), and 206 (67.8%) cases were classified as low NLR and high NLR groups, low PLR and high PLR groups, and low LMR and high LMR groups, respectively. Univariate analysis showed that white blood cell count (WBC), neutrophil count (NEU), platelet count (PLT), NLR, pathologic N stage (pN stage), TNM stage and postoperative complications were significantly associated with OS (p < 0.05). Multivariate analysis showed that NEU, NLR, TNM stage and postoperative complications were independent negative prognostic factors for HNSCC (p < 0.05)., Conclusion: Preoperative NLR is an independent negative prognostic factor for HNSCC. Patients with an increased NLR may have a poor OS., (© 2023. The Author(s).)

Background: Tumor-infiltrating lymphocytes (TILs) by routine hematoxylin and eosin staining (H&E-TILs) are a robust prognostic biomarker in various cancers. However, the role of H&E-TILs in esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CCRT) has not been reported. The purpose of this study was to assess the prognostic value of H&E-TILs in ESCC treated with CCRT., Methods: The clinical data of 160 patients with ESCC treated with CCRT in our center between Jan. 2014 and Dec. 2021 were collected and retrospectively reviewed, and propensity score matching (PSM) analyses were performed. The H&E-TILs sections before CCRT were reassessed by two experienced pathologists independently. The H&E-TILs sections were classified into a positive group (+, > 10%) and a negative group (-, ≤ 10%) using 10% as the cutoff. The effects of H&E-TILs on overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) were explored using the Kaplan‒Meier method, and the log-rank test was used to test the differences. Multivariable analysis was performed using the Cox proportion hazards model., Results: The short-term response to CCRT and the OS (P < 0.001), DMFS (P = 0.001), and LRFS (P < 0.001) rates were significantly different between the H&E-TILs (+) and H&E-TILs (-) groups. Subgroup analysis showed that H&E-TILs(+) with CR + PR group had a longer survival than H&E-TILs(-) with CR + PR, H&E-TILs(+) with SD + PD and H&E-TILs(-) with SD + PD group, respectively(P < 0.001). Furthermore, based on TCGA data, patients in the high TILs group had a better prognosis than those in the low TILs group. Multivariate analyses indicated that H&E-TILs and the short-term response to CCRT were the only two independent factors affecting OS, PFS, DMFS, and LRFS simultaneously, and H&E-TILs expression was associated with an even better prognosis for those patients with CR + PR., Conclusions: H&E-TILs may be an effective and beneficial prognostic biomarker for ESCC patients treated with CCRT. Patients with H&E-TILs (+) with PR + CR would achieve excellent survival. Further prospective studies are required to validate the conclusions., (© 2023. The Author(s).)

Background: Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm affecting infants or young children. KHE includes a spectrum of lesions, ranging from small and superficial tumors to large and invasive lesions with Kasabach-Merritt phenomenon (KMP). Currently, no published studies have reported a KHE presenting as thrombocytopenia and Raynaud phenomenon., Case Presentation: A 2-year-old boy with right hand swelling and thrombocytopenia was admitted to our hospital. His right hand turned swelling and red, even occasionally cyanotic. This condition became worse in response to cool environments and improved with warming, and platelet counts were between 50 ~ 80 × 10^9/L. Physical examination on admission revealed the swelling and frostbite-like rash of the right-hand fingers, and the skin temperature of the right hand was lower than the left. On day 3 of admission, chest CT results showed an irregular mass on the right side of the spine. The puncture biopsy demonstrated positive CD31, D2-40, and FLI1 immunohistochemical staining, but negative GLUT1 staining, confirming the diagnosis of KHE. Furthermore, endothelin-1 (ET1) expression levels significantly increased, and eNOS and A20 expression levels significantly decreased comparing with control patients. The patient received methylprednisolone and sirolimus treatments, and his condition gradually improved during the follow-up., Conclusions: We reported the first case of KHE presenting with thrombocytopenia and Raynaud phenomenon. The development of Raynaud phenomenon could be associated with increased ET-1 and reduced eNOS and A20 expressions. Careful differential diagnosis of hidden KHE should be considered in children with thrombocytopenia and Raynaud phenomenon., (© 2023. The Author(s).)

Background: Ovarian cancer is commonly associated with a poor prognosis due to metastasis and chemoresistance. PINK1 (PTEN-induced kinase 1) is a serine/threonine kinase that plays a crucial part in regulating various physiological and pathophysiological processes in cancer cells., Methods: The ATdb database and "CuratedOvarianData" were used to evaluate the effect of kinases on ovarian cancer survival. The gene expression in ovarian cancer cells was detected by Western blot and quantitative real-time PCR. The effects of gene knockdown or overexpression in vitro were evaluated by wound healing assay, cell transwell assay, immunofluorescence staining, immunohistochemistry, and flow cytometry analysis. Mass spectrometry analysis, protein structure analysis, co-immunoprecipitation assay, nuclear-cytoplasmic separation, and in vitro kinase assay were applied to demonstrate the PINK1-PTEN (phosphatase and tensin homolog) interaction and the effect of this interaction. The metastasis experiments for ovarian cancer xenografts were performed in female BALB/c nude mice., Results: PINK1 was strongly associated with a poor prognosis in ovarian cancer patients and promoted metastasis and chemoresistance in ovarian cancer cells. Although the canonical PINK1/PRKN (parkin RBR E3 ubiquitin protein ligase) pathway showed weak effects in ovarian cancer, PINK1 was identified to interact with PTEN and phosphorylate it at Serine179. Remarkably, the phosphorylation of PTEN resulted in the inactivation of the phosphatase activity, leading to an increase in AKT (AKT serine/threonine kinase) activity. Moreover, PINK1-mediated phosphorylation of PTEN impaired the nuclear import of PTEN, thereby enhancing the cancer cells' ability to resist chemotherapy and metastasize., Conclusions: PINK1 interacts with and phosphorylates PTEN at Serine179, resulting in the activation of AKT and the inhibition of PTEN nuclear import. PINK1 promotes ovarian cancer metastasis and chemotherapy resistance through the regulation of PTEN. These findings offer new potential therapeutic targets for ovarian cancer management., (© 2023. The Author(s).)

Background: Colorectal cancer (CRC) is a prominent global cancer with high mortality rates among human beings. Efficient diagnosis and treatment have always been a challenge for CRC management. Fluorescence guided cancer therapy, which combines diagnosis with therapy into one platform, has brought a new chance for achieving precise cancer theranostics. Among this, photosensitizers, applied in photodynamic therapy (PDT), given the integration of real-time imaging capacity and efficacious treatment feasibility, show great potential to serve as remarkable tools. Although much effort has been put into constructing photosensitizers for locating and destroying CRC cells, it is still in high need to develop novel photosensitizers to attain specific detection and fulfil effective therapy., Methods: Probe HTI was rational synthesized for the diagnosis and treatment of CRC. Spectrometric determination was carried out first, followed by the 1 O 2 generation ability test. Then, HTI was displayed in distinguishing CRC cells from normal cells Further, the PDT effect of the photosensitizer was studied in vitro. Additionally, HTI was used in CRC BALB/c nude mice model to validate its viscosity labelling and tumor suppression characteristics., Results: We successfully fabricated a mitochondrial targeting probe, HTI, together with remarkable viscosity sensitivity, ultralow background interference, and excellent 1 O 2 generation capacity. HTI was favorably applied to the viscosity detection, displaying a 11-fold fluorescent intensity enhancement in solvents from 1.57 cp to 2043 cp. Then, it was demonstrated that HTI could distinguish CRC cells from normal cells upon the difference in mitochondrial viscosity. Moreover, HTI was qualified for producing 1 O 2 with high efficiency in cells, supported by the sparkling signals of DCFH after incubation with HTI under light irradiation. More importantly, the viscosity labelling and tumor suppression performance in CRC CDX model was determined, enriching the multifunctional validation of HTI in vivo., Conclusions: In this study, HTI was demonstrated to show a sensitive response to mitochondrial viscosity and possess a high 1 O 2 generation capacity. Both in vitro cell imaging and in vivo tumor treatment trials proved that HTI was effectively served as a robust scaffold for tumor labeling and CRC cells clearance. This breakthrough discovery held immense potential for advancing the early diagnosis and management of CRC through PDT. By leveraging HTI's properties, medical professionals could benefit from improved diagnostic accuracy and targeted treatment in CRC management, ultimately leading to enhanced patient outcomes., (© 2023. The Author(s).)

Background: Age-associated changes in immunity are inextricably linked to chronic inflammation and age-related diseases, the impact of aging on monocyte subsets is poorly understood., Methods: Flow cytometry was applied to distinguish three monocyte subsets between 120 young and 103 aged individuals. We then analyzed the expression profiles of three monocyte subsets from 9 young and 9 older donors and CD14 + monocytes from 1202 individuals between 44 and 83 years old. Flow cytometry was used to measure β-galactosidase activities, ROS levels, mitochondrial contents, mitochondrial membrane potentials (MMPs) and intracellular IL-6 levels in three monocyte subsets of young and elderly individuals, and plasma IL-6 levels were detected by electrochemiluminescence immunoassay. Mitochondrial stress and glycolytic rate of CD14 + monocytes from young and aged individuals were measured by Seahorse XFe24 Analyzer., Results: Compared with young individuals, the percentage of classical subset in aged persons significantly decreased, while the proportion of nonclassical subset increased. Age-related differential genes were obviously enriched in cellular senescence, ROS, oxidative phosphorylation, mitochondrial respiratory chain, IL-6 and ribosome-related pathways. Compared with young individuals, the β-galactosidase activities, ROS contents, intracellular IL-6 levels of three monocyte subsets, and plasma IL-6 levels in aged individuals were significantly elevated, while the MMPs apparently declined with age and the mitochondrial contents were only increased in intermediate and nonclassical subsets. CD14 + monocytes from elderly adults had conspicuously lower basal and spare respiratory capacity and higher basal glycolysis than those from young individuals., Conclusions: During aging, monocytes exhibited senescence-associated secretory phenotype, mitochondrial dysfunction, decreased oxidative phosphorylation and increased glycolysis and the nonclassical subset displayed the clearest features of aging. Our study comprehensively investigated age-related transcriptional alterations of three monocyte subsets and identified the pivotal pathways of monocyte senescence, which may have significant implications for tactics to alleviate age-related conditions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The application of coagulation-related markers in laryngeal squamous cell carcinoma(LSCC) remains unclear. This study explored the prognostic role of coagulation markers in the progression and metastasis of LSCC., Methods: Coagulation markers of patients with LSCC receiving surgery in the Second Affiliated Hospital of Fujian Medical University in China, from January 2013 to May 2022 were retrospectively analyzed and compared with those of contemporary patients with benign laryngeal diseases. The relationship between clinicopathological features of LSCC and coagulation markers was analyzed with the chi-square and rank sum tests. The ROC curve analysis was utilized to evaluate the diagnostic efficacy of seven coagulation markers for LSCC and its different clinicopathological features, and to find the optimal cutoff value of each coagulation marker., Results: 303 patients with LSCC and 533 patients with benign laryngeal diseases were included in the present analysis. Compared to the control group, prothrombin time (PT) (p < 0.001), activated partial thromboplastin time (APTT) (p = 0.001), and Fib (p < 0.001) in patients with LSCC were significantly higher, while mean platelet volume (MPV) (p < 0.001) was significantly shorter. Significant increases were detected in PT (Z = 14.342, p = 0.002), Fib (Z = 25.985, p < 0.001), platelet count (PC) (Z = 12.768, p = 0.005), PCT (Z = 9.178, p = 0.027), MPV (F = 2.948, p = 0.033) in T4 stage. Fib had the highest prognostic value among the seven coagulation markers in different T stages (AUC = 0.676, p < 0.001), N stages (AUC = 0.717, p < 0.001), tumor stage (AUC = 0.665, p < 0.001), differentiation degree (AUC = 0.579, p = 0.022), and neurovascular invasion (AUC = 0.651, p = 0.007). Fib (Z = 25.832, p < 0.001), PC (Z = 23.842, p < 0.001), and PCT (Z = 20.15, p < 0.001) in N1 and N3 stages were significantly higher than in N0 stage. PT (Z = 12.174, p = 0.007), Fib (Z = 23.873, p < 0.001), PC (Z = 17.785, p < 0.001), and PCT (Z = 14.693, p = 0.002) were significantly higher in stage IV than in stage I and II. APTT (Z=-1.983, p = 0.047), Fib (Z=-2.68, p = 0.007), PC (Z=-2.723, p = 0.006), and PCT (Z=-2.592, p = 0.01) increased significantly when the tumor invaded neurovascular tissue., Conclusions: Coagulation markers have the potential to act as biomarkers for predicting pathological features of LSCC. The high level of Fib was helpful for the diagnosis of LSCC and the detection of advanced LSCC., Trial Registration: Not applicable., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Given the difficulties or incapacity of teeth movement in orthodontic treatment, the ways to speed tooth movement must be investigated. Besides, nonsteroidal anti-inflammatory drugs (NSAIDs) were utilized to treat pain caused by tooth movement during orthodontic treatment. The purpose of this study is to examine the impact of aspirin and low-frequency high-intensity ultrasound (LFHIU) on rat orthodontic tooth movement in rats., Methods: Thirty-six male Sprague-Dawley rats were divided into three groups: orthodontic (O), ultrasound-treated orthodontic (OU), and ultrasound-treated orthodontic with aspirin gavage (OUA) group. In the OU and OUA group, LFHIU (44 W/cm2, 28 kHz) was applied to the buccal side of the maxillary first molar alveolar bone for 10 s every day. In the OUA group, aspirin was given by gavage every day. The rats were sacrificed on days 1, 3, 7, and 14., Results: After ultrasonic treatment, the speed of tooth movement was increased by about 1.5 times. And the number of osteoclasts considerably increased by about 2 times. However, they decreased slightly after aspirin gavage. By Applying ultrasound therapy, Receptor Activator for Nuclear Factor-κ B Ligand (RANKL) levels in periodontal tissue were elevated. Aspirin was able to reduce these increases. Results from Micro Computed Tomography (Micro-CT) revealed that bone mineral density decreased by about 1/5 after ultrasound treatment on the compression side. The rate of bone mineral apposition indicated that bone was forming under tension, and that of the OU group increased by about 1.3 times that O group., Conclusions: Although aspirin slowed this trend, LFHIU still enhanced overall tooth mobility in orthodontic treatment., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: This study aims to explore the impacts of knowledge and attitude on the behavior of antibiotic use during the treatment of the common cold based on the expanding KAP model, and then identify the critical behavioral stage., Methods: A cross-sectional study was conducted on 815 public from 21 community health centers (CHCs) in Chongqing, China. Based on the expanding KAP model, a self-administered questionnaire was designed to measure knowledge, attitude, multi-stage behavior, and perceived threat, in which multi-stage behavior was divided into pre-use antibiotic behavior, during-use antibiotic behavior, and post-use antibiotic behavior. A structural equation model was used to examine the model fit and the direct, indirect, mediating effects, and moderating effect of the variables., Results: The expanding KAP showed good model fit indices with χ²/df = 0.537, RMSEA = 0.033, CFI = 0.973, GFI = 0.971, NFI = 0.934, TLI = 0.979. Knowledge had a positive effect on attitude (β = 0.503, p < 0.05), pre-use antibiotic behavior (β = 0.348, p < 0.05), during-use antibiotic behavior (β = 0.461, p < 0.001), and post-use antibiotic behavior (β = 0.547, p < 0.001). Attitude had a positive effect on during-use antibiotic behavior (β = 0.296, p < 0.001), and post-use antibiotic behavior (β = 0.747, p < 0.001). The mediating effect of attitude was positive among knowledge, during-use antibiotic behavior (β = 0.149, p < 0.05), and post-use antibiotic behavior (β = 0.376, p < 0.001). Perceived threat also had a positive moderating effect between knowledge and post-use antibiotic behavior (β = 0.021, p < 0.001)., Conclusions: Knowledge, attitude and perceived threat had different effects on different stages of antibiotic behavior. The critical behavioral stage prioritized the post-use antibiotic behavior and during-use antibiotic behavior over pre-use antibiotic behavior., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Managing multidrug-resistant (MDR) HIV infections in children is particularly challenging due to the lack of experience with new drugs in the pediatric setting. Second-line albuvirtide (ABT) with an optimized antiretroviral background therapy was approved for adults and adolescents after first-line treatment failure. This paper describes the treatment outcomes and adverse effects of an ABT-based dual-active antiretroviral treatment regimen in a child with MDR HIV strains., Case Presentation: A 13 year-old Chinese female patient infected with MDR HIV strains showed a decrease in viral load (from 4.48 log10 to 1.73 log10) and an increase in CD4 + T cells (from 15 to 308 cells/µl) after 12 months of treatment with an ABT-based antiretroviral regimen. The child showed no relevant drug-related adverse reactions., Conclusions: The case reported here could suggest that an ABT-based antiretroviral therapy might be beneficial and without relevant toxicity in children with MDR HIV. Infectiologists specializing in managing HIV should be prepared to manage an increasing number of children with MDR HIV. ABT might be a new treatment option for MDR HIV infection in children., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Ovarian cancer (OC) is the most malignant tumor with the worst prognosis in female reproductive system. Mitophagy and long non-coding RNAs (lncRNAs) play pivotal roles in tumorigenesis, development, and drug resistance. The effects of mitophagy-related lncRNAs on OC prognosis and therapeutic response remain unelucidated., Methods: We retrieved OC-related RNA sequence, copy number variation, somatic mutation, and clinicopathological information from The Cancer Genome Atlas database and mitophagy-related gene sets from the Reactome database. Pearson's correlation analysis was used to distinguish mitophagy-related lncRNAs. A prognostic lncRNA signature was constructed using UniCox, LASSO, and forward stepwise regression analysis. Individuals with a risk score above or below the median were classified as high- or low-risk groups, respectively. The risk model was analyzed using the Kaplan-Meier estimator, receiver operating characteristic curve, decision curve analysis, and Cox regression analysis and validated using an internal dataset. LINC00174 was validated in clinical samples and OC cell lines. We also reviewed reports on the role of LINC00174 in cancer. Subsequently, a nomogram model was constructed. Furthermore, the Genomics of Drug Sensitivity in Cancer database was used to explore the relationship between the risk model and anti-tumor drug sensitivity. Gene set variation analysis was performed to assess potential differences in biological functions between the two groups. Finally, a lncRNA prognostic signature-related competing endogenous RNA (ceRNA) network was constructed., Results: The prognostic signature showed that patients in the high-risk group had a poorer prognosis. The nomogram exhibited satisfactory accuracy and predictive potential. LINC00174 mainly acts as an oncogene in cancer and is upregulated in OC; its knockdown inhibited the proliferation and migration, and promoted apoptosis of OC cells. High-risk patients were more insensitive to cisplatin and olaparib than low-risk patients. The ceRNA network may help explore the potential regulatory mechanisms of lncRNAs., Conclusion: The mitophagy-related lncRNA signature can help estimate the survival and drug sensitivity, the ceRNA network may provide novel therapeutic targets for patients with OC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Immunocheckpoint inhibitor(ICI) is a major breakthrough in tumor treatment. It can activate the patient's own immune system and play an anti-tumor role, but not all patients can benefit from it. At present, there is still a lack of effective biomarkers to guide clinical application. The systemic immune inflammation(SII) index reflects the systemic inflammatory state and immune state of patients. Prognostic nutrition index(PNI) can be used to evaluate immune status of patients. Therefore, SII and PNI indexes may have some value in predicting the efficacy and prognosis of immunotherapy, but there is still a lack of relevant research. The purpose of our study was to explore the influence of SII and PNI index on the efficacy and prognosis of immunotherapy., Methods: A total of 1935 patients treated with ICIs treatment in the Fourth Hospital of Hebei Medical University from November 2016 to October 2021 were retrospectively collected. 435 patients who met the inclusion criteria and did not meet the exclusion criteria. The imaging data, blood results of each patient were collected within 1 week before ICIs treatment. The neutrophil lymphocyte ratio(NLR), platelet lymphocyte ratio(PLR), monocyte lymphocyte ratio(MLR), PNI,systemic inflammatory response index(SIRI),neutrophil-eosinophil ratio(NER) was calculated. The patients were followed up by in-patient, out-patient reexamination and telephone contact, and the efficacy evaluation and survival status were recorded. The deadline of follow-up: January 2021. SPSS-24.0 software was employed for statistical analysis., Results: Among the 435 patients receiving ICI treatment, 61,236 and 138 patients were evaluated respectively as partial response (PR), stable disease (SD) and progressive disease (PD). The overall response rate(ORR) and disease control rate (DCR) of this cohort were 14.0% and 68.3%, respectively. Median progression-free survival (mPFS) is 4.0 months, The overall survival (mOS) of this cohort is 6.8 months. Multivariate analysis showed that SIRI(Hazard Ratio, HR = 1.304, P = 0.014), PNI (HR = 0.771, P = 0.019), prealbumin (PAB) (HR = 0.596, P = 0.001), and PNI(HR = 0.657, P = 0.008) were independent risk factors for PFS and OS, respectively., Conclusions: Patients with high SIRI value and low PNI value before ICI treatment have shorter PFS. Patients with higher PNI value have better prognosis. Therefore, hematological indicators may become predictors of immunotherapy., (© 2023. The Author(s).)

Background: Autophagy is a critical self-eating pathway involved in numerous physiological and pathological processes. Lysosomal degradation of dysfunctional organelles and invading microorganisms is central to the autophagy mechanism and essential for combating disease-related conditions. Therefore, monitoring fluctuations in the lysosomal microenvironment is vital for tracking the dynamic process of autophagy. Although much effort has been put into designing probes for measuring lysosomal viscosity or pH separately, there is a need to validate the concurrent imaging of the two elements to enhance the understanding of the dynamic progression of autophagy., Methods: Probe HFI was synthesized in three steps and was developed to visualize changes in viscosity and pH within lysosomes for real-time autophagy tracking. Then, the spectrometric determination was carried out. Next, the probe was applied to image autophagy in cells under nutrient-deprivation or external stress. Additionally, the performance of HFI to monitor autophagy was employed to evaluate acetaminophen-induced liver injury., Results: We constructed a ratiometric dual-responsive probe, HFI, with a large Stokes shift over 200 nm, dual-wavelength emission, and small background interference. The ratiometric fluorescent signal (R = I 610 /I 460 ) of HFI had an excellent correlation with both viscosity and pH. More importantly, high viscosity and low pH had a synergistic promotion effect on the emission intensity of HFI, which enabled it to specially lit lysosomes without disturbing the inherent microenvironment. We then successfully used HFI to monitor intracellular autophagy induced by starvation or drugs in real-time. Interestingly, HFI also enabled us to visualize the occurrence of autophagy in the liver tissue of a DILI model, as well as the reversible effect of hepatoprotective drugs on this event., Conclusions: In this study, we developed the first ratiometric dual-responsive fluorescent probe, HFI, for real-time revealing autophagic details. It could image lysosomes with minimal perturbation to their inherent pH, allowing us to track changes in lysosomal viscosity and pH in living cells. Ultimately, HFI has great potential to serve as a useful indicator for autophagic changes in viscosity and pH in complex biological samples and can also be used to assess drug safety., (© 2023. The Author(s).)

Background: Metabolic reprogramming is a critical event for cell fate and function, making it an attractive target for clinical therapy. The function of metabolic reprogramming in Helicobacter pylori (H. pylori)-infected gastric intestinal metaplasia remained to be identified., Methods: Xanthurenic acid (XA) was measured in gastric cancer cells treated with H. pylori or H. pylori virulence factor, respectively, and qPCR and WB were performed to detect CDX2 and key metabolic enzymes expression. A subcellular fractionation approach, luciferase and ChIP combined with immunofluorescence were applied to reveal the mechanism underlying H. pylori mediated kynurenine pathway in intestinal metaplasia in vivo and in vitro., Results: Herein, we, for the first time, demonstrated that H. pylori contributed to gastric intestinal metaplasia characterized by enhanced Caudal-related homeobox transcription factor-2 (CDX2) and mucin2 (MUC2) expression, which was attributed to activation of kynurenine pathway. H. pylori promoted kynurenine aminotransferase II (KAT2)-mediated kynurenine pathway of tryptophan metabolism, leading to XA production, which further induced CDX2 expression in gastric epithelial cells. Mechanically, H. pylori activated cyclic guanylate adenylate synthase (cGAS)-interferon regulatory factor 3 (IRF3) pathway in gastric epithelial cells, leading to enhance IRF3 nuclear translocation and the binding of IRF3 to KAT2 promoter. Inhibition of KAT2 could significantly reverse the effect of H. pylori on CDX2 expression. Also, the rescue phenomenon was observed in gastric epithelial cells treated with H. pylori after IRF3 inhibition in vitro and in vivo. Most importantly, phospho-IRF3 was confirmed to be a clinical positive relationship with CDX2., Conclusion: These finding suggested H. pylori contributed to gastric intestinal metaplasia through KAT2-mediated kynurenine pathway of tryptophan metabolism via cGAS-IRF3 signaling, targeting the kynurenine pathway could be a promising strategy to prevent gastric intestinal metaplasia caused by H. pylori infection. Video Abstract., (© 2023. The Author(s).)

Background: Osteosarcopenia is a syndrome with a concomitant presence of both sarcopenia and osteopenia/osteoporosis. It increases the risk of frailty, falls, fractures, hospitalization, and death. Not only does it burden the lives of older adults, but it also increases the economic burden on health systems around the world. This study aimed to review the prevalence and risk factors of osteosarcopenia to generate important references for clinical work in this area., Methods: Pubmed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, CBM, and VIP databases were searched from inception until April 24th, 2022. The quality of studies included in the review was evaluated using the NOS and AHRQ Scale. Pooled effects of the prevalence and associated factors were calculated using random or fixed effects models. Egger's test, Begg's test, and funnel plots were used to test the publication bias. Sensitivity analysis and subgroup analysis were conducted to identify the sources of heterogeneity. Statistical analysis was performed using Stata 14.0 and Review Manager 5.4., Results: A total of 31 studies involving 15,062 patients were included in this meta-analysis. The prevalence of osteosarcopenia ranged from 1.5 to 65.7%, with an overall prevalence of 21% (95% CI: 0.16-0.26). The risk factors for osteosarcopenia were female (OR 5.10, 95% CI: 2.37-10.98), older age (OR 1.12, 95% CI: 1.03-1.21), and fracture (OR 2.92, 95% CI: 1.62-5.25)., Conclusion: The prevalence of osteosarcopenia was high. Females, advanced age, and history of fracture were independently associated with osteosarcopenia. It is necessary to adopt integrated multidisciplinary management., (© 2023. The Author(s).)

Background: The cerebellum plays key roles in the pathology of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), but the way in which these conditions affect how the cerebellum communicates with the rest of the brain (its connectome) and associated genetic correlates remains largely unknown., Methods: Combining multimodal MRI data from 208 MS patients, 200 NMOSD patients and 228 healthy controls and brain-wide transcriptional data, this study characterized convergent and divergent alterations in within-cerebellar and cerebello-cerebral morphological and functional connectivity in MS and NMOSD, and further explored the association between the connectivity alterations and gene expression profiles., Results: Despite numerous common alterations in the two conditions, diagnosis-specific increases in cerebellar morphological connectivity were found in MS within the cerebellar secondary motor module, and in NMOSD between cerebellar primary motor module and cerebral motor- and sensory-related areas. Both diseases also exhibited decreased functional connectivity between cerebellar motor modules and cerebral association cortices with MS-specific decreases within cerebellar secondary motor module and NMOSD-specific decreases between cerebellar motor modules and cerebral limbic and default-mode regions. Transcriptional data explained > 37.5% variance of the cerebellar functional alterations in MS with the most correlated genes enriched in signaling and ion transport-related processes and preferentially located in excitatory and inhibitory neurons. For NMOSD, similar results were found but with the most correlated genes also preferentially located in astrocytes and microglia. Finally, we showed that cerebellar connectivity can help distinguish the three groups from each other with morphological connectivity as predominant features for differentiating the patients from controls while functional connectivity for discriminating the two diseases., Conclusions: We demonstrate convergent and divergent cerebellar connectome alterations and associated transcriptomic signatures between MS and NMOSD, providing insight into shared and unique neurobiological mechanisms underlying these two diseases., (© 2023. The Author(s).)

Background: Venetoclax (Ven) combined with intensive chemotherapy was proven effective in the management of acute myeloid leukemia (AML). However, the severe and prolonged myelosuppression remains a concern to worry about. To explore more appropriate combination regimens, we designed Ven combining daunorubicin and cytarabine (DA 2 + 6) regimen as induction therapy, aimed to evaluate the effectiveness and safety in adults de novo AML., Methods: A phase 2 clinical trial was performed in 10 Chinese hospitals to investigate Ven combined with daunorubicin and cytarabine (DA 2 + 6) in patients with AML. The primary endpoints were overall response rate (ORR), comprising of complete remission (CR), complete remission with incomplete blood cell count recovery (CRi), and partial response (PR). Secondary endpoints included measurable residual disease (MRD) of bone marrow assessed by flow cytometry, overall survival (OS), event-free survival (EFS), disease-free survival (DFS), and the safety of regimens. This study is a currently ongoing trial listed on the Chinese Clinical Trial Registry as ChiCTR2200061524., Results: Overall, 42 patients were enrolled from January 2022 to November 2022; 54.8% (23/42) were male, and the median age was 40 (range, 16-60) years. The ORR after one cycle of induction was 92.9% (95% confidence interval [CI], 91.6-94.1; 39/42) with a composite complete response rate (CR + CRi) 90.5% (95% CI, 89.3-91.6, CR 37/42, CRi 1/42). Moreover, 87.9% (29/33) of the CR patients with undetectable MRD (95% CI, 84.9-90.8). Grade 3 or worse adverse effects included neutropenia (100%), thrombocytopenia (100%), febrile neutropenia (90.5%), and one mortality. The median neutrophil and platelet recovery times were 13 (5-26) and 12 (8-26) days, respectively. Until Jan 30, 2023, the estimated 12-month OS, EFS, and DFS rates were 83.1% (95% CI, 78.8-87.4), 82.7% (95% CI, 79.4-86.1), and 92.0% (95% CI, 89.8-94.3), respectively., Conclusion: Ven with DA (2 + 6) is a highly effective and safe induction therapy for adults with newly diagnosed AML. To the best of our knowledge, this induction therapy has the shortest myelosuppressive period but has similar efficacy to previous studies., (© 2023. The Author(s).)

Introduction: The results of laboratory testing are crucial basis for clinicians to prescribe antimicrobial. Laboratory testing is a highly complex process, and increasing evidence suggests that errors and obstacles in the pre-analytical process (PP) will affect reasonable antimicrobial use. However, PP was an easily neglected link in hospital infection management and the current situation of it and the influencing factors of management are not clear., Methods: A cross-sectional survey was conducted in the department of clinical, specimen collection, transportation, and inspection in 109 secondary and tertiary hospitals in Central China. The rate of antimicrobial susceptibility test request (AST) and related indexes of above departments were calculated to describe the situation. Management characteristics (frequency of training etc.) were described as proportions and fractional probit regression analysis was used to determine the influencing factors., Results: The average rate of non restricted-use antimicrobial was 63%, the restricted-use was 86%, the special-use was 95%. The zero obstacle rate of specimen collection was 27.3%, of specimen transportation was 19.4% and of inspection feedback was 61.7%. There was a difference between the secondary and tertiary hospitals on non restricted-use (X 2  = 22.968, P < 0.001); restricted-use (X 2  = 29.466, P < 0.001); special-use (X 2  = 27.317, P < 0.001). Taking non restricted-use as an example, training (OR = 0.312, 95%CI: 0.148,0.429), low-frequency appraisal (OR = 0.153, 95%CI: 0.082,0.224), guidance (OR = 0.32, 95%CI: 0.237,0.403) and information technology (OR = 0.104, 95%CI: 0.009,0.199) were positive factors., Conclusions: There were substantial differences in the rate of AST request in clinical department between secondary and tertiary hospitals. The zero obstacle rate in collection, transportation and inspection department were still low. In most departments, training and performance appraisal were positive factors, guidance and information technology were positive supporting factors., (© 2023. The Author(s).)

Background: Macroautophagy is an essential cellular self-protection mechanism, and defective autophagy has been considered to contribute to a variety of diseases. During the process, cytoplasmic components are transported via autophagosomes to acidic lysosomes for metabolism and recycling, which represents application niches for lysosome-targeted fluorescent probes. Additionally, in view of the complexity of the autophagy pathway, it entails more stringent requirements for probes suitable for monitoring autophagy. Meanwhile, aggregation-induced emission (AIE) fluorescent probes have been impressively demonstrated in the biomedical field, which bring fascinating possibilities to the autophagy visualization., Methods: We reported a generalizable de novo design of a novel pH-sensitive AIE probe ASMP-AP tailored to lysosome targeting for the interpretation of autophagy. Firstly, the theoretical calculation was carried out followed by the investigation of optical properties. Then, the performance of ASMP-AP in visualizing autophagy was corroborated by starvation or drugs treatments. Furthermore, the capability of ASMP-AP to monitor autophagy was demonstrated in ex vivo liver tissue and zebrafish in vivo., Results: ASMP-AP displays a large stokes shift, great cell permeability and good biocompatibility. More importantly, ASMP-AP enables a good linear response to pH, which derives from the fact that its aggregation state can be manipulated by the acidity. It was successfully applied for imaging autophagy in living cells and was proved capable of monitoring mitophagy. Moreover, this novel molecular tool was validated by ex vivo visualization of activated autophagy in drug-induced liver injury model. Interestingly, it provided a meaningful pharmacological insight that the melanin inhibitor 1-phenyl-2-thiourea (PTU)-induced autophagy was clearly presented in wild-type zebrafish., Conclusions: ASMP-AP offers a simple yet effective tool for studying lysosome and autophagy. This is the first instance to visualize autophagy in zebrafish using a small-molecule probe with AIE characters, accurate lysosome targeting and simultaneous pH sensitivity. Ultimately, this novel fluorescent system has great potential for in vivo translation to fuel autophagy research., (© 2023. The Author(s).)

Background: Atherosclerosis (AS) is a chronic disease characterized by abnormal blood lipid metabolism, inflammation and vascular endothelial injury. Vascular endothelial injury is the initial stage during the occurrence of AS. However, the function and mechanism of anti-AS are not well characterized. Danggui-Shaoyao-San (DGSY) is a classic Traditional Chinese Medicine (TCM) prescription for the treatment of gynecological diseases, and has been widely used in the treatment of AS in recent years., Methods: ApoE -/- atherosclerosis male mice were established by feeding with high-fat diet, and then randomly divided into three groups: Atherosclerosis group (AS), Danggui-Shaoyao-San group (DGSY), and Atorvastatin calcium group (X). The mice were administered with the drugs for 16 weeks. Pathological changes in aortic vessels were examined by staining with Oil red O, Masson and hematoxylin-eosin. In addition, blood lipids were analyzed. The level of IL-6 and IL-8 in aortic vessels were detected by ELISA and the expression of ICAM-1 and VCAM-1 in the aortic vascular endothelium were measured by Immunohistochemical. The mRNA expression of interα5β1/c-Abl/YAP in the aortic vessels were measured by Real-time quantitative PCR and location of expression was assessed by immunofluorescence., Results: DGSY can significantly reduce the content of TC,TG and LDL-C and increase the level of HDL-C in the serum, reduce the plaque area and inhibit the concentration of IL-6 and IL-8, down-regulate the expression of IVAM-1,VCAM-1 and interα5β1/ c-Abl/YAP in the aortic vessels., Conclusions: Collectively, DGSY can alleviate vascular endothelium damage and delay the occurrence of AS, and the underlying mechanism may be related to the multi-target protective of DGSY., (© 2023. The Author(s).)

Background: Circular RNAs (circRNAs) have important regulatory functions in cancer, but the role of circRNAs in the tumor microenvironment (TME) remains unclear. Moreover, we also explore the effects of si-circRNAs loaded in nanoparticles as therapeutic agent for anti-tumor in vivo., Methods: We conducted bioinformatics analysis, qRT-PCR, EdU assays, Transwell assays, co-culture system and multiple orthotopic xenograft models to investigate the expression and function of circRNAs. Additionally, PLGA-based nanoparticles loaded with si-circRNAs were used to evaluate the potential of nanotherapeutic strategy in anti-tumor response., Results: We identified oncogene SERPINE2 derived circRNA, named as cSERPINE2, which was notably elevated in breast cancer and was closely related to poor clinical outcome. Functionally, tumor exosomal cSERPINE2 was shuttled to tumor associated macrophages (TAMs) and enhanced the secretion of Interleukin-6 (IL-6), leading to increased proliferation and invasion of breast cancer cells. Furthermore, IL-6 in turn increased the EIF4A3 and CCL2 levels within tumor cells in a positive feedback mechanism, further enhancing tumor cSERPINE2 biogenesis and promoting the recruitment of TAMs. More importantly, we developed a PLGA-based nanoparticle loaded with si-cSERPINE2, which effectively attenuated breast cancer progression in vivo., Conclusions: Our study illustrates a novel mechanism that tumor exosomal cSERPINE2 mediates a positive feedback loop between tumor cells and TAMs to promote cancer progression, which may serve as a promising nanotherapeutic strategy for the treatment of breast cancer., (© 2023. The Author(s).)

Background: With the increasing morbidity and mortality of preeclampsia (PE), it has posed a huge challenge to public health. Previous studies have reported endoplasmic reticulum (ER) stress could contribute to trophoblastic dysfunction which was associated with the N 6 -methyladenosine (m 6 A) modification by methyltransferase-like 3 (METTL3), resulting in PE. However, little was known about the relationship between METTL3 and ER stress in PE. Thus, in vitro and in vivo studies were performed to clarify the mechanism about how METTL3 affects the trophoblasts under ER stress in PE and to explore a therapeutic approach for PE., Methods: An ER stress model in HTR-8/SVneo cells and a preeclamptic rat model were used to study the mechanism and explore a therapeutic approach for PE. Western blot, immunohistochemistry, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and methylated RNA immunoprecipitation (MeRIP)-qPCR were performed to detect the protein, RNA, and methylated transmembrane BAX inhibitor motif containing 6 (TMBIM6) expression levels. The m 6 A colorimetric and mRNA stability assays were used to measure the m 6 A levels and TMBIM6 stability, respectively. Short hairpin RNAs (shRNAs) were used to knockdown METTL3 and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Flow cytometry and Transwell assays were performed to evaluate the apoptosis and invasion abilities of trophoblasts., Results: Upregulated METTL3 and m 6 A levels and downregulated TMBIM6 levels were observed in preeclamptic placentas under ER stress. The ER stress model was successfully constructed, and knockdown of METTL3 had a beneficial effect on HTR-8/SVneo cells under ER stress as it decreased the levels of methylated TMBIM6 mRNA. Moreover, overexpression of TMBIM6 was beneficial to HTR-8/SVneo cells under ER stress as it could neutralize the harmful effects of METTL3 overexpression. Similar to the knockdown of METTL3, downregulation of YTHDF2 expression resulted in the increased expression and mRNA stability of TMBIM6. Finally, improved systemic symptoms as well as protected placentas and fetuses were demonstrated in vivo., Conclusions: METTL3/YTHDF2/TMBIM6 axis exerts a significant role in trophoblast dysfunction resulting in PE while inhibiting METTL3 may provide a novel therapeutic approach for PE., (© 2023. The Author(s).)

Background: Major concerns about the adverse mental health impact of the rapidly spread COVID-19 pandemic have been raised. Previous studies on changes of depressive symptoms during the COVID-19 pandemic have yielded inconsistent results regarding the sex differences. Since women have higher depressive symptoms even without the pandemic, it is essential to consider the pre-existing change of depressive symptoms of a similar period to discern the effect of the pandemic on depression. This study aimed to evaluate sex differences in depressive symptoms before and during the pandemic., Methods: Data from the Health and Retirement Study (HRS; waves 13 to 15) and the English Longitudinal Study of Ageing (ELSA; wave 8 to COVID-19 wave 2) were analyzed. Depressive symptoms were assessed by the 8-item Center for Epidemiological Studies Depression (CES-D) scale. According to the time of COVID-19 outbreak in the US and the UK, the intervals from waves 13 to 14 surveys of the HRS and from waves 8 to 9 surveys of the ELSA were employed as pre-pandemic periods to control for the pre-existing depressive symptoms, respectively. Changes of CES-D scores during the pre-pandemic and pandemic periods were assessed by linear mixed models., Results: Nine thousand, seven hundred thirty-seven participants (mean age: 66.7 ± 10.7 years) from the HRS and 5,098 participants (mean age: 68.7 ± 10.0 years) from the ELSA were included. CES-D scores among women were significantly higher than those among men at all waves in both cohorts. During the pre-pandemic period, no significant sex difference on changes of CES-D scores was detected in either the HRS or the ELSA. During the pandemic period, CES-D scores were increased in both men and women and the sex differences in CES-D increments of the two cohorts were both significant. Enlarged sex differences were demonstrated in increments of CES-D scores during the pandemic period., Conclusions: Our results suggest women suffered from worse depressive symptoms in response to the pandemic, although the changes of depression were similar between men and women before the pandemic. These findings underscore the necessity to support the vulnerable populations, especially women, to manage the distress brought by the pandemic and maintain optimal mental health status., (© 2023. The Author(s).)