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Abstract Purpose The prevalence of biliary tract diseases, which are common gastrointestinal disorders, is steadily rising. If it progresses to sepsis or septic shock, it can endanger the patient's life. Therefore, it is crucial to promptly diagnose bacterial infection in individuals suffering from biliary diseases and comprehend the risk factors associated with infection. The objective of this study was to examine the types of bacteria present in the bile of patients with biliary tract diseases, assess any alterations in their susceptibility to antimicrobial agents, and identify the risk factors contributing to the development of infection in these patients. Patients and methods From June 2019 to November 2022, 317 patients of biliary tract diseases with positive bile culture were included in this hospital-based descriptive analysis. The hospital's computerized medical records were used to collect data on demographic information (including gender, age, and occupation), laboratory, and clinical findings, physical examination results, comorbidities, basic diseases, treatment history, complications, and in-hospital outcomes. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) principles. Results Of the 317 patients with positive biliary tract diseases, 247 had benign diseases and 70 had malignant diseases. Patients with benign disease experienced a higher prevalence of statistically significant symptoms such as abdominal pain (81.4% vs. 57.1%, P = 0.000), nausea (31.2% vs. 14.3%, P = 0.005), vomiting (30.0% vs. 12.9%, P = 0.004), and chills (10.9% vs. 2.9%, P = 0.039), while jaundice (12.6% vs. 37.1%, P = 0.000) was more common in patients with malignant disease. At the species level, Escherichia coli (105; 40.5%), Klebsiella pneumoniae (41; 15.8%), and Pseudomonas aeruginosa (30; 11.6%) were the most commonly found Gram-negative bacterial strains in biliary tract infection. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were most susceptible to tigecycline, ertapenem and ceftazidime/avibactam, respectively. Conclusion Gram-negative bacteria are the most commonly isolated biliary bacteria. Clinical doctors should pay attention to patients with malignant diseases with low hemoglobin, high total bilirubin and high alkaline phosphatase. Carbapenems, tigecycline, and minocycline are the recommended antibiotics for Enterobacteriaceae. In recent years, the proportion of enterococcus has gradually increased, and clinical attention should be paid to enterococcus infection. Linezolid and vancomycin were recommended for the treatment of Enterococci infections. Overall, this work can provide reference for clinical diagnosis, treatment and effective interventions.

PurposeLiver hepatocellular carcinoma (LIHC) is the most common type of liver cancer, but there is a lack of effective indicators for its early diagnosis and prognosis, so we explored the role of KEAP1 in LIHC patients in this study.MethodsThe Cancer Genome Atlas (TCGA) dataset was used to investigate the relationship between KEAP1 expression and clinicopathological features and prognosis of LIHC patients. KEAP1 expression related pathways were enriched by Gene Ontology (GO) and gene set enrichment analysis (GSEA). Besides, KEAP1 expression-related immune infiltration was performed by single-sample GSEA (ssGSEA), and function of immune cells was detected by flow cytometry.ResultsIt was found that KEAP1 expression was significantly increased and correlated with overall survival of LIHC patients. A total of 231 differentially expressed genes (DEGs) between LIHC patients with high- and low-KEAP1 expression were found, which associated with various biological pathways. Besides, KEAP1 expression was positively correlated with the infiltration level of T helper cells and Th2 cells but negatively correlated with DCs and cytotoxic cells. Functional analysis revealed that the expression of IL 4 in Th2 cells and CD107a, GrA and GrB in cytotoxic cells was significantly greater in LIHC patients than in HCs. In addition, KEAP1 expression was closely correlated with liver function in LIHC patients.ConclusionHighly expressed KEAP1 was closely related to the diagnosis, prognosis, immune cell infiltration, and liver function of LIHC, which might promote the progression of LIHC through regulating cell development, signal transduction, and abnormal immune response. The current study partially revealed the role of KEAP1 in LIHC and provided a potential biomarker for the diagnosis, prognosis and treatment of LIHC.

We determined RNA spectrum of the human RSK4 (hRSK4) gene (also called RPS6KA6) and identified 29 novel mRNA variants derived from alternative splicing, which, plus the NCBI-documented ones and the five we reported previously, totaled 50 hRSK4 RNAs that, by our bioinformatics analyses, encode 35 hRSK4 protein isoforms of 35–762 amino acids. Many of the mRNAs are bicistronic or tricistronic for hRSK4. The NCBI-normalized NM_014496.5 and the protein it encodes are designated herein as the Wt-1 mRNA and protein, respectively, whereas the NM_001330512.1 and the long protein it encodes are designated as the Wt-2 mRNA and protein, respectively. Many of the mRNA variants responded differently to different situations of stress, including serum starvation, a febrile temperature, treatment with ethanol or ethanol-extracted clove buds (an herbal medicine), whereas the same stressed situation often caused quite different alterations among different mRNA variants in different cell lines. Mosifloxacin, an antibiotics and also a functional inhibitor of hRSK4, could inhibit the expression of certain hRSK4 mRNA variants. The hRSK4 gene likely uses alternative splicing as a handy tool to adapt to different stressed situations, and the mRNA and protein multiplicities may partly explain the incongruous literature on its expression and comports.

Cancer cells subvert multiple properties of normal cells, including escaping strict cell cycle regulation, gaining resistance to cell death, and remodeling the tumor microenvironment. The hallmarks of cancer have recently been updated and summarized. Nuclear factor erythroid 2-related factor 1 (NFE2L1, also named NRF1) belongs to the cap’n’collar (CNC) basic-region leucine zipper (bZIP) family. It acts as a transcription factor and is indispensable for maintaining both cellular homoeostasis and organ integrity during development and growth, as well as adaptive responses to pathophysiological stressors. In addition, NFE2L1 mediates the proteasome bounce-back effect in the clinical proteasome inhibitor therapy of neuroblastoma, multiple myeloma, and triple-negative breast cancer, which quickly induces proteasome inhibitor resistance. Recent studies have shown that NFE2L1 mediates cell proliferation and metabolic reprogramming in various cancer cell lines. We combined the framework provided by “hallmarks of cancer” with recent research on NFE2L1 to summarize the role and mechanism of NFE2L1 in cancer. These ongoing efforts aim to contribute to the development of potential novel cancer therapies that target the NFE2L1 pathway and its activity.

Abstract Objective To investigate the clinical significance and value of peripheral blood T lymphocyte subset in patients with asymptomatic novel coronavirus variant strains infection (OMICRON). Methods A retrospective analysis of 281 patients with asymptomatic OMICRON infection who were admitted and isolated to the Fuyang Second People's Hospital from March to April 2022 was conducted. With 32 normal people as the control group, T lymphocytes of the two groups (CD3 + T, CD3 + CD4 + T, CD3 + CD8 + T) were analyzed and the differences between the two groups were analyzed. CD4 + T lymphocytes between patients with asymptomatic OMICRON infection and patients with mild COVID-19 infection in 2020 were analyzed and compared. Based on CD3 CD4 + T lymphocyte changes, lymphocyte reference range: CD3 CD4 + T lymphocyte count 404–1612/μL. Lower than 404 × 106/μL was defined as lymphocytopenia, patients were divided into the reduced group (138) and the normal group (143). The CT value of novel coronavirus nucleic acid (ORF1ab gene, N gene) and the time of viral shedding were compared between the two groups. Results Differences in number of CD3 + T cells, CD3 + CD4 + T cells, and CD3 + CD8 + T cells were significant between both groups (P

Sea buckthorn (Hippophae rhamnoides) is an important dioecious tree species of protective plantation with insufficiently documented on the sexual responses difference to environmental stress as well as the interaction between sexual competition and heavy metal stress. In order to provide the practical guidance for repairing heavy metal pollution in soil, the physiological responses and tolerance of male and female sea buckthorn plants under Mn stress and different sexual competition interaction patterns were discussed. The physiological responses of sea buckthorn under Mn stress (4 000 mg·kg-1) and three different sexual combinations (female × female, male × male, female × male) were determined, including the contents of chlorophyll, peroxidase (POD), superoxide dismutase (SOD), malondialdehyde (MDA), total phenols (TP), free proline (Pro), soluble sugar (SS), glycine betaine (GB) and manganese in male and female leaves. The results were as follows：(1) Under Mn stress, the SOD of male plants (M/FM) was the highest in all competition combinations, while the MDA content was not significantly increased compared with the control, indicating that the male plants had better antioxidant capacity and less membrane oxidative damage. (2) M/FM accumulated more free proline and showed better osmotic adjustment ability under Mn stress, indicating that male plants under sexual competition showed better tolerance to Mn stress. (3) The study indicated that male-female interaction and Mn stress interaction significantly affected the physiological response characteristics of sea buckthorn leaves, such as chlorophyll content, antioxidant enzyme activity and osmotic adjustment. Principal component analysis showed that the contents of SOD, POD, MDA, chlorophyll b (Chlb), SS and Pro in leaves could be used as the main physiological response indicators. The results can be used as a reference for the remediation of soil heavy metal pollution by sea buckthorn plants.

Objective: The aim of this research is to synthesize and evaluate β-amyloid (Aβ) binding probes for early diagnosis of Alzheimer's disease (AD). Methods: We designed and synthesized two new fluorine tag Indanone derivatives (compounds a and b), and then based on the platform of ultra-high-performance liquid chromatography-mass spectrometry for its affinity with β-amyloid (Aβ) protein determination, and use of compounds a and b solution as dyes for AD brain tissue staining in vitro. To evaluate the lipid solubility and stability of the drug, the lipid-water partition coefficient was determined using n-octanol as the lipid phase, and the stability of compound b was tested in vitro to mimic the in vivo environment. Results: Both compounds a and b exhibit high affinity for binding to Aβ. The Kd values of compound a for Aβ1-40 and Aβ1-42 were found to be 467.40 ± 63.26, and 227.57 ± 19.08 nmol/L, respectively. Similarly, the Kd values of compound b for Aβ1-40 and Aβ1-42 were 438.13 ± 26.77 and 167.27 ± 23.70 nmol/L, respectively. In the staining experiment of human brain slices of AD, both compounds a and b were found to bind to Aβ plaques, and their staining effect was stronger than positive control (0.1 % ThS). In the lipid-water partition coefficient experiment, compound a and compound b exhibited logP values of 0.84 and 1.85, respectively, indicating good lipid solubility. In the in vitro stability experiment, compound b exhibited a concentration of 74.79 %, 80.47 %, and 70.00 % after incubation in liver, brain homogenate, and blood, respectively. Conclusion: We have successfully designed and synthesized two probes labeled with fluoride that can be used for diagnosing AD. These probes have a high affinity for Aβ protein and good lipid solubility. As A contrast agent based on Aβ protein, compound b showed greater potential than compound a.

PurposeThis study aimed to evaluate the use of serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in the diagnosis of Alzheimer’s disease (AD) and the differential diagnosis between AD and mild cognitive impairment (MCI).MethodsFrom September 2021 to October 2022, we collected venous blood from patients and healthy individuals who visited our hospital’s Neurology Department, and we isolated serum to detect NfL and GFAP using direct chemiluminescence. The results were analyzed using one-way analysis of variance (ANOVA) analysis and receiver operating characteristic (ROC) curves.ResultsPairwise comparisons among the three groups showed that compared with the health checkup (HC) group, serum NfL and GFAP were increased in both AD and MCI (PNfL 40.09 pg./mL and GFAP >31.40 pg./mL. Sensitivity and specificity for NfL in the diagnosis of AD were 59.6 and 76.2%, respectively, and for GFAP, they were 90.4 and 82.1%, respectively. The combined diagnosis of GFAP and NfL improved the diagnostic efficiency (AUC = 0.931, sensitivity = 78.8%, specificity = 92.3%). The cut-off value of GFAP for the differential diagnosis of MCI and AD was 46.05 pg./mL.ConclusionBoth serum NfL and serum GFAP can be used as biomarkers for the diagnosis of AD. Serum GFAP has better diagnostic efficacy and can distinguish AD from MCI. A combined diagnosis can improve diagnostic specificity.

Summary: Influenza A virus (IAV) remains a pressing global health concern, yet our understanding of the specific nature and functional roles of certain circulating cell subsets in relation to this viral infection remains unclear. We performed single-cell RNA sequencing (scRNA-seq) on single-cell whole-blood (scWB) isolated from various populations using the Singleron Matrix platform. Our investigation showed a significant upregulation of the IFN-stimulated gene, IFN-α-inducible protein 27 (IFI27), in patients affected by IAV infection and further found that the heightened expression of IFI27 was primarily concentrated in specific immune cell populations, including monocytes and conventional dendritic cells (cDCs). Notably, we identified a specific subset of neutrophils, neutrophil_ISG15, which implicates interferon (IFN) signaling in IAV infection. Our findings provide a comprehensive understanding of the cellular subtypes and molecular characteristics of scWB across different populations with IAV infection.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality. Early identification of patients who may advance to critical stages is crucial. This investigation aimed to establish models to predict SFTS before it reaches the critical illness stage. Methods: Between January 2016 and September 2022, 278 cases have been included in this study. There were 87 demographic and systemic chosen variables. For selecting the predictive variables from the cohort, the LASSO was utilized, and for identifying independent predictors, multivariate logistic regression was performed. Based on these factors, a nomogram was established for critical illness. Concordance index values, decision curve analysis and the area under the curve (AUC) were also examined. Results: Multivariate logistic regression demonstrated the most important differentiating factors as;> 65 years old (P

IntroductionAlthough previous research found that small-sided game (SSG) training was more enjoyable than high-intensity interval training (HIT) in various sports, no data were provided during longer training period in basketball. Furthermore, the comparison of internal loads between the two training approaches needs to be further examined. Thus, this study aimed to examine the acute physiological, perceived exertion and enjoyment responses during 4-week progressive basketball SSG or HIT programs.MethodsNineteen female collegiate basketball players were randomly assigned to two groups that performed either HIT (n = 10) or SSG (n = 9) 3 times per week for 4 continuous weeks. Average and percentage of maximal heart rate (HRmean and %HRmax), rating of perceived exertion (RPE), and physical activity enjoyment (PACES) were determined during each training session.ResultsThere was a main group effect in PACES (p 90% of HRmax) for female basketball players.

In this paper, the robustness of a system with sundry disturbed open loop dynamics is investigated by employing robust right coprime factorization (RRCF). These sundry disturbed open loop dynamics are present not only in the feed forward path, but also within the feedback loop. In such a control framework, the nominal plant is firstly right coprime factorized and a feed forward and a feedback controllers are designed based on Bezout identity to ensure the overall stability. Subsequently, considering the sundry disturbed open loop dynamics, a new condition formulated as a disturbed Bezout identity is put forward to achieve the closed loop stability of the system, even in the presence of disturbances existing in sundry open loops, where in the feedback loop a disturbed identity operator is defined. This approach guarantees the system robustness if a specific inequality condition is satisfied. And, it should be noted that the proposed approach is applicable to both linear and nonlinear systems with sundry disturbed open loop dynamics. Simulations demonstrate the effectiveness of our methodology.

Abstract Background Metastasis of malignant tumors accelerates systemic failure and hastens the deaths of pancreatic cancer patients. During the metastatic process, the physical translocation of cancer cells from the primary lesion to distant organs and is crucial. CSCs properties, such as self-renewal and multiple-direction differentiation capacity are essential for colonization in the microenvironment of distant organs and metastatic lesion formation. It is widely believed that EMT can cause cancer cells to penetrate blood vessels by undergoing phenotypic and cytoskeletal changes, so that they can infiltrate surrounding tissue and disseminate from the primary tumor to the blood circulation, where they are termed circulating tumor cells (CTCs), while CTCs often exhibit stemness properties. Accumulating evidence demonstrates that some EMT-related transcription factors are essential for CSCs self-renewal, so cancer cells that have undergone EMT typically acquire increased stemness properties. Abnormal activation of the WNT signaling pathway can drive a series of gene transcripts to promote EMT in multiple types of cancer, and among different Frizzled receptors of WNT signaling pathway, FZD7 expression is associated with distant organ metastasis, advanced clinical stages, and poor clinical prognosis. Objective of this study is to demonstrate that high FZD7 expression in pancreatic cancer can accelerate hepatic metastases and elucidate the related molecular mechanisms. Methods The expression of Frrizled receptor 7 (FZD7) in pancreatic ductal adenocarcinoma (PDAC) and relating survival rate were analyzed by bioinformatics, histochemistry assay and follow-up study. In vitro, FZD7 expression was silenced by lentiviral vectors carrying short hair RNA (shRNA) or upregulated by overexpression plasmid. Then, Wound-healing and Transwell experiment was used to analyze the abilities of migration and invasion; the levels of epithelial-to-mesenchymal transition (EMT) relating phenotype proteins, stemness relating phenotype proteins, and signaling molecular proteins were measured by Western-blot; cell stemness was evaluated by sphere forming ability of cells in suspension culture and detecting the proportion of CD24+CD44+ cells with flow cytometry. TGF-β1 was used to induce EMT, and observe the effect of shRNA silencing FZD7 on which. Results High level of FZD7 expression in pancreatic cancer samples was associated with earlier hepatic metastasis. In vitro upregulation FZD7 can enable pancreatic cancer cells to obtain stronger migration and invasion ability and higher mesenchymal phenotype, and vice versa; the proportion of cancer stem cell (CSC) was also positively correlated with the level of FZD7; cells forming spheres in suspension culture showed stronger migration and invasion ability and higher level of mesenchymal phenotype than normal adherent cultured cells; the level of FZD7 was positively correlated with the level of activated β-catenin. Silencing FZD7 expression can attenuate EMT induced by TGF-β1 stimulating, and TGF-β1 stimulating can also upregulate stemness phenotype expression, such as ABCG2, CD24, and CD44 by mediating of FZD7. Conclusions High FZD7 expression in pancreatic cancer can accelerates hepatic metastases by promoting EMT and strengthening cell stemness, and FZD7 can work through the canonical Wingless-type (WNT) signaling pathway and participate in TGF-β/SMAD3 signaling pathway also.

BackgroundBacterium/fungus-associated pneumonia (BAP/FAP) is the prominent cause of high mortality and morbidity with important clinical impacts globally. Effective diagnostic methods and proper specimen types hopefully facilitate early diagnosis of pneumonia and prevent spread of drug-resistant bacteria/fungi among critically ill patients.MethodsIn the present study, 342 bronchoalveolar lavage fluid (BALF) samples were collected from critically ill patients with pulmonary infections between November 2020 and March 2021. The BALF materials were comparatively employed to screen BAP/FAP through microscopy, culture, antigenic marker and PCR-based methods. The limit of detection (LOD) of cultures and PCR for bacteria/fungi was determined by serial dilution assays. Specimen slides were prepared with Gram staining for microscopic examinations. Microbial cultures and identifications underwent routine clinical protocols with the aid of mass spectrometry. (1,3)-β-D-glucan and galactomannan tests with BALF were carried out accordingly. Direct detection of pathogens in BALF was achieved through PCR, followed by sequencing and BLAST in GenBank database for pathogenic identification. The subjects’ demographic and clinical characteristics were well evaluated.ResultsBAP/FAP was identified in approximately 47% of the subjects by the BALF-based PCR. The PCR-based diagnostic methods showed improved detection performance for fungi with good LOD, but performed similarly for bacteria, when compared to the cultures. There was poor agreement among traditional microscopy, culture and PCR assays for bacterial detections (kappa value, 0.184 to 0.277). For overall bacterial/fungal detections, the microscopy showed the lowest detecting rate, followed by the cultures, which displayed a slightly higher sensitivity than the microscopy did. The sensitivity of PCR was much higher than that of the other means of interest. However, the traditional cultures rather than antigenic marker-based approaches were moderately consistent with the PCR-based methods in fungal species identification, particularly for Candida and Aspergillus spp. Our findings further revealed that the age, length of hospital stay, invasive procedures and cerebral diseases were likely considered as main risk factors for BAP/FAP.ConclusionScreening for BALF in critically ill patients with suspected pneumonia pertaining high risk factors using combined PCR-based molecular detection strategies would hopefully contribute to early diagnosis of BAP/FAP and improved prognosis of the patients.

Abstract Abnormal expression of 5-Lipoxygenase Activating Protein (FLAP) has been detected in many tumor cells. MicroRNAs (miRNAs) negatively regulate gene expression post-transcriptionally by binding to the 3'–untranslated region (3'–UTR) of the target mRNA sequences and have been shown to be involved in various types of cancers. Herein, we aimed to demonstrate the expression of miR-146a and FLAP in human HCC tissues and liver cancer cell lines. We demonstrated that miR-146a expression is overexpressed, while FLAP protein and mRNA are suppressed in hepatocellular carcinoma tissues and HepG2 cells compared to para-carcinoma tissues and HL–7702 cells. Dual luciferase reporter gene assay showed that miR-146a-5p can directly target FLAP mRNA. Knockdown of miR-146a also resulted in increased FLAP expression of cancer cells. Additionally, miR-146a silencing or restoration of FLAP led to a reduction of HepG2 cell proliferation, cell cycle progression, migration, and invasion. This study showed that miR-146a has a stimulatory role in HepG2 cells and promotes HepG2 cell migration and invasion by targeting FLAP mRNA. Thus, miR-146a may be a tumor promoter and a potential therapeutic target for the treatment of HCC patients.

Abstract N 6-Methyladenosine (m6A), the most abundant internal modification associated with eukaryotic mRNAs, has emerged as a dynamic regulatory mechanism controlling the expression of genes involved in many physiological activities by affecting various steps of mRNA metabolism, including splicing, export, translation, and stability. Here, we review the general role of m6A, highlighting recent advances related to the three major types enzymes that determine the level of m6A modification (i.e., writers, erasers, and readers) and the regulatory mechanism by which m6A influences multiple stages of RNA metabolism. This review clarifies the close connection and interaction between m6A modification and nuclear gene expression, and provides key background information for further studies of its roles in numerous physiological and pathophysiological processes. Among them, perhaps the most eye-catching process is tumorigenesis. Clarifying the molecular mechanism of tumorigenesis, development and metastasis in various tissues of the human body is conducive to curbing out-of-control cell activities from the root and providing a new strategy for human beings to defeat tumors.

BackgroundBloodstream infections (BSIs), especially hospital-acquired BSIs, are a major cause of morbidity and mortality. However, the details about the pathogens and antimicrobial resistance profile of BSIs across China are still lacking.MethodsAn investigation was conducted in 10 large teaching hospitals from seven geographic regions across China in 2016 based on China Antimicrobial Surveillance Network (CHINET) to profile the clinical and etiological features of BSIs.ResultsA total of 2,773 cases of BSIs were identified, a majority (97.3%) of which were monomicrobial. Overall, 38.4% (1,065/2,773) were community-acquired BSIs (CABSIs), and 61.6% (1,708/2,773) were hospital-acquired BSIs (HABSIs). Of the 2,861 pathogenic BSI isolates, 67.5% were Gram-negative bacteria, 29.6% were Gram-positive bacteria, and 2.9% were fungi. The top BSI pathogens were Escherichia coli, Klebsiella pneumoniae, coagulase-negative Staphylococci (CNS), Staphylococcus aureus, Enterococci, and Acinetobacter baumannii. Escherichia coli and K. pneumoniae isolates showed low susceptibility to penicillins, cephalosporins (except ceftazidime and cefepime), and ampicillin-sulbactam (13.1%–43.4% susceptible); moderate susceptibility (about 60% susceptible) to ceftazidime, cefepime, and aztreonam; and high susceptibility (>90%) to β-lactam/β-lactamase inhibitor combinations other than ampicillin-sulbactam, except K. pneumoniae strains to piperacillin-tazobactam (59.2% susceptible). HABSIs were associated with significantly higher prevalence of carbapenem-resistant and extended-spectrum β-lactamases-producing K. pneumoniae, methicillin-resistant S. aureus, methicillin-resistant CNS, and ampicillin-resistant Enterococci than CABSIs. Overall, 42.0% of the BSI due to S. aureus strains were resistant to methicillin.ConclusionsThe findings about BSIs in teaching hospitals across China add more scientific evidence to inform the appropriate management of the disease.

To study the potential relationship between melatonin and beta‐amyloid (Abeta), we established a liquid chromatography–mass spectrometry (LC‐MS) method to quantitatively analyze melatonin, deuterated isotopes (melatonin‐D4), and internal standard 6‐iodo‐2‐(4'‐dimethylamino‐) phenyl‐imidazo(1,2) pyridine (IMPY) under positive (+) mode. The gradient elution was set to 6 min, and the corresponding peak time of melatonin and its isotope melatonin‐D4 was 3.14 min, while the peak time for the internal standard IMPY was 3.24 min. Next, we established and optimized the molecule receptor saturation binding assay based on LC‐MS to determine the melatonin affinity for beta‐amyloid (Abeta). Melatonin showed a high and specific binding for Abeta. The corresponding equilibrium dissociation constant (Kd) of melatonin with Abeta 1‐40 and Abeta 1‐42 was 814.37 ± 36.62 and 628.33 ± 13.57 nmol·L−1; besides, the Kd of melatonin with mixed plaques (1‐40 and 1‐42) was 461.13 ± 45.37 nmol·L−1. The results may suggest the potential mechanism of action of MT on Abeta and provide a theoretical basis for the improvement of MT treatment of Alzheimer's disease.

BackgroundElizabethkingia meningoseptica is a bacterium causing potential nosocomial infections and is associated with a high mortality rate; however, the date of patients in the Hefei population who have been diagnosed with this infection is generally limited.PurposeThe clinical and laboratory data of patients from a tertiary hospital in Hefei City who had E. meningoseptica infection were evaluated in this retrospective analysis.Patients and methodsFrom May 2017 to November 2021, there were 24 patients infected with E. meningoseptica in the First Affiliated Hospital of Anhui Medical University. Data were gathered from the hospital's electronic medical records for all patients.ResultsThe most prevalent symptom among the 24 patients was fever (83.3%), followed by edema (41.7%), cough (37.5%), altered consciousness (41.7%), and sputum (37.5%), and laboratory results presented with anemia (75%), hypoproteinemia (75%), elevated C-reactive protein (CRP) (66.7%), neutrophilia (54.2%), and leukocytosis (50.0%). Hepatic disease (1 vs. 7, P = 0.009) was the only significant risk factor for underlying diseases. The mean value of lymphocyte (LYMPH#) (1.4 vs. 0.83 × 109/L, P = 0.033) counts was higher in the survival group than death group, while both anemia (8 vs. 10, P = 0.024) and hypoproteinemia (8 vs. 10, P = 0.024) occurred more frequently in the death group compared with the survival one.ConclusionFever was the most common symptom and the only significant factor of underlying diseases was hepatic disease (P = 0.009) that often occurred in death groups. In this investigation, the risk factors for death in patients were anemia, hypoproteinemia, and lymphocyte count. The susceptibility of some quinolones, piperacillin-tazobactam, and cotrimoxazole was relatively high, suggesting that they may be the preferred drugs for the treatment of E. meningoseptica infection. As E. meningoseptica can produce biofilm to pollute the hospital environment and cause infection in patients, the disinfection of the hospital environment should be strengthened and medical staff should pay attention to aseptic operations.

Abstract Objective To identify the correlation between the level of at-admission fasting blood glucose (FBG) with poor outcomes in hospitalized patients suffering from severe fever with thrombocytopenia syndrome (SFTS). Methods Between April 1 and December 1, 2020, the list of hospitalized patients affected with SFTS infection was provided by the Infectious Disease Department at First Affiliated Hospital of Anhui Medical University, followed by the collection of information I.e., gender, age, diabetic history and the level of FBG on admission. Results In this study, a total of 77 patients were included and were categorized into three groups (

Abstract Background m6A is the most prevalent and abundant form of mRNA modifications and is closely related to tumor proliferation, differentiation, and tumorigenesis. In this study, we try to conduct an effective prediction model to investigated the function of m6A RNA methylation modulators in pancreatic adenocarcinoma and estimated the potential association between m6A RNA methylation modulators and tumor microenvironment infiltration for optimization of treatment. Methods Expression of 28 m6A RNA methylation modulators and clinical data of patients with pancreatic adenocarcinoma and normal samples were obtained from TCGA and GTEx database. Differences in the expression of 28 m6A RNA methylation modulators between tumour (n = 40) and healthy (n = 167) samples were compared by Wilcoxon test. LASSO Cox regression was used to select m6A RNA methylation modulators to analyze the relationship between expression and clinical characteristics by univariate and multivariate regression. A risk score prognosis model was conducted based on the expression of select m6A RNA methylation modulators. Bioinformatics analysis was used to explore the association between the m6Ascore and the composition of infiltrating immune cells between high and low m6Ascore group by CIBERSORT algorithm. Evaluation of m6Ascore for immunotherapy was analyzed via the IPS and three immunotherapy cohort. Besides, the biological signaling pathways of the m6A RNA methylation modulators were examined by gene set enrichment analysis (GSEA). Results Expression of 28 m6A RNA methylation modulators were upregulated in patients with PAAD except for MTEEL3. An m6Ascore prognosis model was established, including KIAA1429, IGF2BP2, IGF2BP3, METTL3, EIF3H and LRPPRC was used to predict the prognosis of patients with PAAD, the high risk score was an independent prognostic indicator for pancreatic adenocarcinoma, and a high risk score presented a lower overall survival. In addition, m6Ascore was related with the immune cell infiltration of PAAD. Patients with a high m6Ascore had lower infiltration of Tregs and CD8+T cells but a higher resting CD4+ T infiltration. Patients with a low m6Ascore displayed a low abundance of PD-1, CTLA-4 and TIGIT, however, the IPS showed no difference between the two groups. The m6Ascore applied in three immunotherapy cohort (GSE78220, TCGA-SKCM, and IMvigor210) did not exhibit a good prediction for estimating the patients’ response to immunotherapy, so it may need more researches to figure out whether the m6A modulator prognosis model would benefit the prediction of pancreatic patients’ response to immunotherapy. Conclusion Modulators involved in m6A RNA methylation were associated with the development of pancreatic cancer. An m6Ascore based on the expression of IGF2BP2, IGF2BP3, KIAA1429, METTL3, EIF3H and LRPPRC is proposed as an indicator of TME status and is instrumental in predicting the prognosis of pancreatic cancer patients.

Abstract Background Pneumocystis pneumonia (PcP), which is caused by Pneumocystis carinii, is a life-threatening infection that affects immunocompromised individuals. Unfortunately, chemoprophylaxis and dapsone are only effective for half of the patients with PcP, indicating that additional preventive methods are needed. We predicated the pneumocystis surface protein A12 sequence 1–85 by DNAStar software and BepiPred, and identified it as a potential vaccine candidate by bioresearch. Methods We used recombinant A121–85 as antigen to immunized mice and detected serum titer of IgG, expression of inflammatory factors by EILSA, qRT-PCR and flow cytometry. Results Our results showed that immunization with recombinant A121–85 increased the serum titer of IgG, promoted the secretion of T lymphocytes, increased the expression of inflammatory factors, and elevated lung inflammatory injury in mice. Conclusions Our findings suggest that A121–85 is a potential vaccine target for preventing Pneumocystis carinii. The evaluation of A121–85-elicited antibodies in the prevention of PcP in humans deserves further investigation.

Abstract Growing evidence indicates that circular RNAs (circRNAs) are closely involved in tumorigenesis, but the association between circRNAs and pancreatic ductal adenocarcinoma (PDAC) is far from clear. Here, we focused on the functional investigation of circ-0005105, a newly identified circRNA, in PDAC progression. In the present study, we assessed circ-0005105 expression in PDAC tissues and cell lines with quantitative reverse transcription–polymerase chain reaction (qRT-PCR). The biological functions of circ-0005105 in cellular proliferation and invasion were identified through gain- and loss-of-function experiments in vitro and in vivo. The interaction between circ-0005105 and the microRNA (miR)-20a-3p–COL11A1 (collagen type XI alpha 1) axis was examined using luciferase reporter and RNA immunoprecipitation assays. We found that circ-0005105 expression was upregulated in both PDAC tissues and cell lines. Higher circ-0005105 expression correlated positively with the malignant clinical phenotype and poor prognosis of patients with PDAC. Gain- and loss-of-function analysis showed that circ-0005105 facilitated both in vitro and in vivo cellular proliferation and invasion. Mechanistically, circ-000510 served as a competing endogenous RNA (ceRNA) of miR-20a-3p and indirectly modulated COL11A1 expression, leading to activation of epithelial–mesenchymal transition (EMT). Rescue experiments suggested that the oncogenic activity of circ-0005105 was dependent on the modulation of the miR-20a-3p–COL11A1 axis. More importantly, COL11A1 overexpression was significantly associated with poor prognosis in PDAC, and silencing COL11A1 reduced PDAC cell tumorigenicity and metastasis. Taken together, our findings confirm for the first time that circ-0005105 has critical functions by regulating the miR-20a-3p–COL11A1 axis. In the clinic, circ-0005105 can act as a potential prognostic marker and therapeutic target in PDAC.

Objective: To investigate the application value of bone marrow megakaryocyte count, the proportion of megakaryocytes at each stage, and the platelet parameter in the clinical diagnosis of primary immune thrombocytopenia (ITP). Methods: The megakaryocyte and platelet parameter level in 62 ITP and 40 control group patients were compared and analyzed. Linear correlation analysis, Pearson correlation analysis, and ROC curves were performed for the correlation between megakaryocytes and platelet parameters. Results: Compared to the control group, the total number of megakaryocytes, the promegakaryocytes the granular megakaryocytes (GMeg), and naked megakaryocytes (NMeg), MPV, and P-LCR% in the ITP group increased. All differences were statistically significant ( P

The most recent human coronaviruses including severe acute respiratory syndrome coronavirus-2 causing severe respiratory tract infection and high pathogenicity bring significant global public health concerns. Infections are initiated by recognizing host cell receptors by coronavirus spike protein S1 subunit, and then S2 mediates membrane fusion. However, human coronavirus spikes undergo frequent mutation, which may result in diverse pathogenesis and infectivity. In this review, we summarize some of these recent structural and mutational characteristics of RBD of human coronavirus spike protein and their interaction with specific human cell receptors and analyze the structural requirements and plasticity of RBD. Stability of spike protein, affinity toward receptor, virus fitness, and infectivity are the factors controlling the viral tropisms. Thus, understanding the molecular details of RBDs and their mutations is critical in deciphering virus evolution. Structural information of spike and receptors of human coronaviruses not only reveals the molecular mechanism of host–microbe interaction and pathogenesis but also helps develop effective drug to control these infectious pathogens and cope with the future emerging coronavirus outbreaks.

The antiviral response of natural killer (NK) cells and CD8+ T cells is weak in patients with chronic hepatitis B (CHB) infection. However, the specific characteristics of these cells and the association between NK cells and CD8+ T cell dysfunction is not well known. In this study, higher galectin-9 (Gal-9) expression was observed in circulating NK cells from CHB patients than from healthy controls and was found to contribute to NK cell dysfunction. In addition, circulating CD8+ T cells showed obvious dysfunction and overexpressed TIM-3, the natural receptor of Gal-9, during active CHB infection. Gal-9+ and Gal-9- NK cells from active CHB patients were sorted and cocultured with autologous CD8+ T cells. The proportion of tetramer+CD8+ T cells and the cytokines production of CD8+ T cells were lower after cocultivation with Gal-9+ than with Gal-9- NK cells. We showed that in vitro depletion of NK cells increased circulating hepatitis B virus (HBV)-specific CD8+ T cell responses in patients with active CHB infection. Because Gal-9 is increased in the serum of CHB patients, CD8+ T cells were sorted and cultured with exogenous Gal-9, resulting in lower IFN-γ, TNF-α, CD107a, and granzyme B levels, decreased expression of the activation receptor CD69, increased expression of TIM-3, and a high percentage of early apoptotic CD8+ T cells. Blocking Gal-9 or TIM-3 in vitro in a culture of peripheral blood mononuclear cells (PBMCs) stimulated with HBV peptide from active CHB patients restored CD8+ T cell function. However, blocking Gal-9 in vitro after removal of NK cells from PBMCs did not rescue CD8+ T cells exhaustion. Furthermore, NK and CD8+ T cells from active CHB patients were sorted and cocultured in vitro, and the exhaustion of CD8+ T cells were alleviated after blocking Gal-9 or TIM-3. In summary, overexpression of Gal-9 on NK cells, which interacts with TIM-3+CD8+ T cells and likely contributes to antiviral CD8+ T cell dysfunction, may be a potential target for the treatment of CHB patients.

Bacteremia caused by Herbaspirillum huttiense (H. huttiense) is relatively rare in positive blood cultures. H. huttiense is an opportunistic bacterium in patients with cancer and cirrhosis and has also been described in immunocompromised hosts. In this study, H. huttiense was isolated from a patient with repeated chest tightness and chest pain. Smears were prepared, stained, and examined by microscopy. Single colonies were analyzed by Gram staining, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), 16S rRNA sequencing and Next-Generation Sequencing (NGS). Antibiotic sensitivity was assessed by agar dilution. Almost all publications on H. huttiense infections in the PubMed/ScienceDirect/EBSCO databases were reviewed and summarized. Blood sample culturing yielded white, gelatinous, and slightly raised colonies without hemolytic rings. The bacilli were found to be Gram-negative, and MS results showed 99.2% homology with H. huttiense. This was confirmed by 16S rRNA gene sequencing, phylogenetic tree analysis and NGS all of which were homologous with H. huttiense in GenBank. Antibiotic susceptibility tests were performed to determine the minimum inhibitory concentrations (MICs) of imipenem, meropenem, piperacillin-tazobactam, and levofloxacin. A comprehensive literature review revealed that H. huttiense was an emergent pathogen. After medical treatment, the patient’s body temperature returned to normal. This is the first report of bacteremia caused by H. huttiense in China. The findings could improve the awareness and attention of the rare pathogenic microorganisms in China.

BackgroundThe phenomenon of co-infection with multiple carbapenem-resistant bacteria is growing, which pose a great challenge for infection control and treatment. This study aimed to analyze predictors of occurrence and 30-day mortality for carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Acinetobacter baumannii co-infection.MethodsFrom June 2018 to June 2021, clinical data of 103 patients co-infected with carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Klebsiella pneumoniae (CRKP) were collected from a tertiary teaching hospital in Anhui Province, China. The clinical characteristics and predictors of mortality were analyzed. Meanwhile, the bacterial isolates were characterized for drug susceptibility, multi-locus sequence typing, and drug resistance genes.ResultsThe multivariate analysis revealed that fiberoptic bronchoscopy (p = 0.005, OR=2.72), repeat transfusions (p = 0.008, OR= 2.23) and exposure to tigecycline (p = 0.002, OR = 6.58) were independent risk factors for CRKP and CRAB co-infection. Neutrophil ≥11.9*109 (p = 0.035, adjusted HR = 3.12) and C-reactive protein ≥ 149 mg/L (p = 0.009, adjusted HR = 4.41) were found associated with 30-day mortality. Combined neutrophil with C-reactive protein could predict 30-day mortality, of which AUC value was 0.791 (95%CI: 0.661-0.921). KPC (46/51, 90.2%) was the most common carbapenemase in CRKP. 33 isolates of CRKP belong to ST11 (33/51, 64.7%), and three new ST types ST5882, ST5883, ST5885 were detected.ConclusionsInvasive operations and antibiotics exposure can lead to CRKP and CRAB co-infection. Combined neutrophil with C-reactive protein could predict 30-day mortality.

Abstract Mining databases and data obtained from assays on human specimens had shown that Fzd7 is closely associated with Wnt7b, that Fzd7/Wnt7b expression is upregulated in pancreatic cancer tissues compared with normal tissues, and its expression is negatively correlated with survival. Fzd7/Wnt7b knockdown in Capan‐2 and Panc‐1 cells reduced the proliferative capacity of pancreatic cancer stem cells (PCSCs), reduced drug resistance, decreased the percentage of CD24+CD44+ subset of cells and the levels of ABCG2, inhibited cell‐sphere formation, and reduced gemcitabine (GEM) resistance. In contrast, Fzd7/Wnt7b overexpression increased the percentage of the CD24+CD44+ subset of cells, and increased the levels of ABCG2 detected in cell spheroids. The gem‐resistant cells exhibited higher levels of Fzd7/Wnt7b expression, an increased percentage of CD24+CD44+ cells, and higher levels of ABCG2 compared with the parental cells. Taken together, Fzd7/Wnt7b knockdown can reduce PDAC cell stemness and chemoresistance by reducing the percentage of CSCs. Mechanistically, Fzd7 binds with Wnt7b and modulates the levels of β‐catenin, and they may exert their role via modulation of the canonical Wnt pathway.

Pancreatic cancer (PC) is one of the malignant tumors with the worst prognosis worldwide because of a lack of early diagnostic markers and efficient therapies. Integrin, beta-like 1 (ITGBL1) is a β-integrin-related extracellular matrix protein and is reported to promote progression of some types of cancer. Nevertheless, the function of ITGBL1 in PC is still not clear. Herein, we found that ITGBL1 was highly expressed in PC tissues compared to normal tissues (P

BackgroundThis study aimed to investigate the Aspergillus species distribution, antifungal sensitivities, clinical characteristics, and risk factors of patients with invasive aspergillosis (IA) in a tertiary teaching hospital in Anhui Province.MethodsIn the present study, 156 Aspergillus isolates were collected from patients admitted to a 2,800-bed comprehensive hospital between January 2019 and April 2021. The epidemiology of Aspergillus species was well-examined, and its antifungal susceptibility was specifically measured by the microbroth dilution method. The risk factors of patients with IA were documented and analyzed intensively. In addition, gene sequencing was employed to determine gene mutations of cytochrome P450 14-α sterol demethylase-Aspergillus (cyp51A) associated with azole resistance among Aspergillus fumigatus.ResultsThe Aspergillus species distribution was dominated by A. fumigatus (56.41%), Aspergillus flavus (20.51%), and Aspergillus niger (15.38%) locally. In particular, all Aspergillus species showed very low minimum inhibitory concentrations (MICs, ≤ 0.5 μg/ml) for azoles and echinocandins, slightly high MICs (1.66–2.91 μg/ml) for amphotericin B, and exceptionally high MICs (>64 μg/ml) for flucytosine. Azole-resistant rate of Aspergillus species in this local region reached up to 5.79%. Correlation analyses of multiple antifungals indicate a significant MIC relevance between isavuconazole and voriconazole (Pearson correlation coefficient was 0.81, P < 0.0001). The clinical risk factors for patients with IA were found primarily to be pulmonary diseases (P = 0.007) and patients' age (P < 0.001). Notably, three mutant loci (TR46/Y121F/T289A) of the cyp51A gene were identified in azole-resistant A. fumigatus.ConclusionsThe Aspergillus species emerged increasingly, of which A. fumigatus and A. flavus remained the main pathogens for invasive Aspergillus infections in the local region. The vast majority of Aspergillus species exhibited good susceptibility to all the antifungals, except flucytosine. The local occurrence of azole-resistant Aspergillus species grew gradually and needed monitoring in time. Pulmonary diseases and age were likely considered as highly associated risk factors for IA. To our knowledge, the clinically isolated azole-resistant A. fumigatus with TR46/Y121F/T289A mutations identified here were rarely reported in the area of China.

Type 2 diabetes mellitus (T2DM) is characterized by high blood glucose levels and chronic low-grade inflammation. It shows a strong association with obesity and immune dysfunction, which makes T2DM patients more susceptible to infectious diseases. NK cells play an important role in pathogen control and tumor surveillance. However, whether NK cell distribution and functional status are altered in T2DM is unclear. To address this issue, we compared surface receptor expression and cytokine production between peripheral blood NK cells from 90 T2DM patients and 62 age- and sex-matched healthy controls. We found a significantly lower frequency and absolute number of NK cells in patients than in controls. Interestingly, the expression of inhibitory receptor Tim-3 was significantly increased, while the expression of the activating receptor NKG2D was significantly decreased, in T2DM NK cells. Both TNF-α secretion and degranulation capacity (evidenced by CD107a expression) were dampened in NK cells from patients. The expression of Tim-3 on NK cells correlated positively with both HbA1c and fasting blood glucose levels and negatively with the percentage and absolute number of total NK cells and was associated with increased NK cell apoptosis. In addition, Tim-3 expression on NK cells negatively correlated with TNF-α production, which could be restored by blocking Galectin-9/Tim-3 pathway. Our results suggest that NK cell dysfunction secondary to augmented Tim-3 expression occurs in T2DM patients, which may partly explain their increased susceptibility to cancer and infectious disease.

Introduction: Interleukin (IL)-1β, as a key biomarker and mediator of vascular calcification in patients with end-stage renal disease (ESRD), may be involved in the process of premature senescence of vascular smooth muscle cells (VSMCs). This work sought to investigate whether IL-1β-induced premature senescence contributes to the process of osteoblastic transition and vascular calcification in VSMCs. Methods: Eighty-eight patients with ESRD (aged 25–81 years), 11 healthy individuals, and 15 cases of lesion-free distal radial arteries from dialysis ESRD patients with angiostomy were collected in this study. Immunohistochemical analysis was performed to detect expression of IL-1β, p21, and bone morphogenetic protein-2 (BMP2) in the distal radial arteries. Primary human VSMCs from healthy neonatal umbilical cords were incubated with test agents for 1–3 days. Intracellular levels of reactive oxygen species (ROS) and senescence-associated-β-galactosidase (SA-β-gal) staining were used to detect senescent cells. Alizarin red staining and the calcium content of the cell layer were used to detect mineral deposition in VSMCs. Results: Coincident with positive staining of IL-1β, p21, and BMP2 in the lesion-free distal radial arteries, 66.67% patients showed mineral deposition. Serum IL-1β was 0.24 ± 0.57, 1.20 ± 2.95, and 9.41 ± 40.52 pg/mL in 11 healthy individuals, 20 patients without calcification, and 53 patients with calcification, respectively. Analysis of the cross-table chi-square test showed cardiovascular calcification is not correlated with levels of serum IL-1β in patients with ESRD (p = 0.533). In response to IL-1β, VSMCs showed a senescence-like phenotype, such as flat and enlarged morphology, increased expression of p21, an increased activity of SA-β-gal, and increased levels of ROS. IL-1β-induced senescence of VSMCs was required for the activation of IL-1β/NF-κB/p53/p21 signaling pathway. IL-1β-induced senescent VSMCs underwent calcification due to osteoblastic transition mainly depending upon the upregulation of BMP2. Resveratrol, an activator of sirtuin-1, postponed the IL-1β-induced senescence through blocking the NF-κB/p53/p21 pathway and attenuated the osteoblastic transition and calcification in VSMCs. Conclusions: High levels of IL-1β in medial smooth muscles of arteries may play roles in inducing senescence-associated calcification. IL-1β-induced senescence depending on the activation of the NF-κB/p53/p21 signaling pathway and contributing to osteoblastic transition of VSMCs.

BackgroundSevere fever with thrombocytopenia syndrome (SFTS), a widely prevalent infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV) that carries with it a high mortality rate, has emerged to be a public health concern. This study aimed to investigate the epidemiological and clinical characteristics of patients infected with SFTSV, seeking novel prognostic risk factors for SFTS.MethodsIn this retrospective and cross-sectional study, confirmed SFTS patients from the First Affiliated Hospital of Anhui Medical University were enrolled from September 1, 2019, to December 12, 2020. Cases were analyzed for epidemiological, demographic, clinical, and laboratory data. Logistic regression models were used to assess the association between predictors and outcome variables. A generalized additive mixed model (GAMM) was conducted to analyze the trending shift of aspartate aminotransferase/alanine transaminase-ratio (AST/ALT-ratio) and platelet (PLT) in SFTS patients treated with ribavirin. p values ≤ 0.05 were considered statistically significant.ResultsClinical and laboratory results of 107 hospitalized patients with SFTSV infection were retrospectively described. The mean age at onset of disease was 60.38 ± 11.29 years old and the ratio between male and female was 1:1.2. Fever and thrombocytopenia are hallmark features of SFTS. Furthermore, multiple cases also experienced neurological complications, gastrointestinal/skeletal muscle symptoms together with other non-specific clinical manifestations; laboratory dataset outcomes reported dysregulated levels for routine blood biomarkers, coagulation function, and biochemistry. Overall, 107 patients were segregated into two groups according to patient condition at the clinical endpoint (survivors/non-survivors). SFTS survivors had a higher level of PLT- counts, total protein (TP), and estimated glomerular filtration rate (eGFR), while levels of activated partial thromboplastin time (APTT), thrombin time (TT), D-dimer (D-D), fibrinogen degradation products (FDP), ALT, AST, AST/ALT-ratio, creatinine (Cr), creatine phosphokinase (CK) and procalcitonin (PCT) was higher in non-survivors. Results from univariate Cox regression revealed that elevated levels of FDP, TT, AST/ALT-ratio, PCT, as well as decreased eGFR level and presence of central nervous system symptoms (CNS), were significant predictors for SFTS prognostic, results from multivariate logistic regression analysis in three adjusted models showed AST/ALT-ratio and PCT were independent risk factors for the prognosis of SFTS patients. Kaplan–Meier survival analysis showed that SFTS patients with AST/ALT-ratio >2.683 were associated with a shorter futime (means survival time), therefore indicating an unfavorable prognosis. Treatment with ribavirin could increase PLT count while decreasing AST/ALT-ratio within SFTS patients.ConclusionSFTS is an emerging infectious disease, possibly leading to multiple-organ injury; AST/ALT-ratio was an independent risk factor for the prognosis of SFTS patients. Further investigation should be performed in order to gain more knowledge on this disease and guide clinical management.

Small molecular dyes are commonly used for bacterial imaging, but they still meet a bottleneck of biological toxicity and fluorescence photobleaching. Carbon dots have shown high potential for bio-imaging due to their low cost and negligible toxicity and anti-photobleaching. However, there is still large space to enhance the quantum yield of the carbon quantum dots and to clarify their mechanisms of bacterial imaging. Using carbon dots for dyeing alive bacteria is difficult because of the thick density and complicated structure of bacterial cell walls. In this work, both dead or alive bacterial cell imaging can be achieved using the primary amine functionalized carbon dots based on their small size, excellent quantum yield and primary amine functional groups. Four types of carbon quantum dots were prepared and estimated for the bacterial imaging. It was found that the spermine as one of precursors can obviously enhance the quantum yield of carbon dots, which showed a high quantum yield of 66.46% and high fluorescence bleaching-resistance (70% can be maintained upon 3-h-irradiation). Furthermore, a mild modifying method was employed to bound ethylenediamine on the surface of the spermine–carbon dots, which is favorable for staining not only the dead bacterial cells but also the alive ones. Investigations of physical structure and chemical groups indicated the existence of primary amine groups on the surface of spermine–carbon quantum dots (which own a much higher quantum yield) which can stain alive bacterial cells visibly. The imaging mechanism was studied in detail, which provides a preliminary reference for exploring efficient and environment-friendly carbon dots for bacterial imaging.

Freezing of gait is a disabling symptom with a complex episodic nature that is frequently experienced by people with Parkinson's disease (PD). Although China has the largest population with PD in the world, no Chinese version of the freezing of gait questionnaire (FOGQ), the instrument that has been most widely used to assess FOG, has yet been developed. This study aimed to translate and adapt the original version of FOGQ to create a Chinese version, the FOGQ-CH, then assess its reliability, calculate the Minimal Detectable Change (MDC) and investigate its validity. The forward-backwards translation model was adopted, and cultural adaptation included expert review and pretesting. For the reliability study, 31 Chinese native speaking patients with PD were assessed two times in a 7–10 days interval. Internal consistency and test-retest reliability of the FOGQ-CH were measured by Cronbach's alpha (Cα) and the Intraclass Correlation Coefficient (ICC). For the validity study, 34 native speakers of Chinese with PD were included. To explore the convergent validity, relationships between the FOGQ-CH and the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) and Part III (UPDRS III), Timed Up and Go Test (TUGT), Timed Up and Go Test in cognitive task (TUGT-Cog), walking speed (10 MWT speed), and step length (10 MWT step length) in a 10-m Walk Test were tested. To explore predictive validity, the number of falls followed up for 6 months were assessed. The area under the ROC curve (AUC) was employed to test the capacity of FOGQ-CH to discriminate those with falls. From the reliability study, Cα = 0.823, ICC = 0.786. The MDC0.90 = 4.538. From the validity study, the FOGQ-CH showed moderate correlations with UPDRS II (rho = 0.560, p = 0.001), UPDRS III (rho = 0.451, p = 0.007), TUGT (rho = 0.556, p = 0.007), TUGT-Cog (rho = 0.557, p = 0.001), 10MWT-speed (rho = −0.478, p = 0.004), 10MWT-step length (rho = −0.419, p = 0.014), and the number of falls followed up for 6 months (rho = 0.356, p = 0.045). The AUC = 0.777 (p = 0.036) for predicting whether the participants will have multiple falls (two or more) in the following 6 months. The FOGQ-CH showed good reliability and validity for assessing Chinese native speaking patients with PD. In addition, the FOGQ-CH showed good efficacy for predicting multiple falls in the following 6 months.

Background: Magnetic seizure therapy (MST) is a potential alternative to electroconvulsive therapy (ECT). However, reports on the use of MST for patients with schizophrenia, particularly in developing countries, which is a main indication for ECT, are limited.Methods: From February 2017 to July 2018, 79 inpatients who met the DSM-5 criteria for schizophrenia were randomized to receive 10 sessions of MST (43 inpatients) or ECT (36 inpatients) over the course of 4 weeks. At baseline and 4-week follow-up, the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to assess symptom severity and cognitive functions, respectively.Results: Seventy-one patients who completed at least half of the treatment protocol were included in the per-protocol analysis. MST generated a non-significant larger antipsychotic effect in terms of a reduction in PANSS total score [g = 0.17, 95% confidence interval (CI) = −0.30, 0.63] and response rate [relative risk (RR) = 1.41, 95% CI = 0.83–2.39]. Twenty-four participants failed to complete the cognitive assessment as a result of severe psychotic symptoms. MST showed significant less cognitive impairment over ECT in terms of immediate memory (g = 1.26, 95% CI = 0.63–1.89), language function (g =1.14, 95% CI = 0.52–1.76), delayed memory (g = 0.75, 95% CI = 0.16–1.35), and global cognitive function (g = 1.07, 95% CI = 0.45–1.68). The intention-to-treat analysis generated similar results except for the differences in delayed memory became statistically insignificant. Better baseline cognitive performance predicted MST and ECT response.Conclusions: Compared to bitemporal ECT with brief pulses and age-dose method, MST had similar antipsychotic efficacy with fewer cognitive impairments, indicating that MST is a promising alternative to ECT as an add-on treatment for schizophrenia.Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT02746965.

Purpose: The current explored the impact of heat inactivation of blood samples on the results of a particular clinical test and its potential application value during the SARS-CoV-2 pandemic. We have aimed at providing a reference for clinical testing methods during the pandemic.Methods: Blood samples were selected from our department's routine clinical examination between January 2021 and June 2021. The levels of these samples for quantitative detection of these indicators in each group (n = 90 cases/group) covered normal reference ranges and medically determined levels. For qualitative testing of the indicators, the specimens were additionally classified as negative, weakly positive, and positive (n = 20 cases/group). The specimens were then inactivated, and the differences in relevant indicators before and after inactivation were evaluated.Results: A statistically significant difference was evident between the levels of TSH, T3, FT4, FT3, AFP, NSE, CYFRA211, IRI, IL-1β, IL-6, IL-8, IL-10, IL-2R, and TNF-α in the non-inactivated group 1 and the inactivated group 1 (P < 0.05). Among them, there was a strong correlation between TSH, T3, FT4, FT3, CYFRA211, IRI, IL-1β, IL-6, IL-8, and IL-2R levels in the two groups (P < 0.05), however, there was no correlation between AFP (P = 0.256) and NSE (P = 0.352) levels between the two groups (P > 0.05). The detected values of low-level AFP ( 0.05). The positive rate of anti-nuclear antibodies after inactivation was not statistically different from the ones observed before inactivation (P > 0.05). Upon correction by the regression equation, the observed levels of TSH, T3, FT4, FT3, CYFRA211, IRI, IL-1β, IL-6, IL-8, and IL-2R were not significantly different from those before inactivation (P > 0.05).Conclusion: The heat inactivation of blood samples had different various effects on different test indicators, and some indicators could be corrected by employing regression equations. This detection method could potentially be employed during the SARS-CoV-2 pandemic, thereby effectively preventing iatrogenic infections.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system was originally discovered in prokaryotes and functions as part of the adaptive immune system. The experimental research of many scholars, as well as scientific and technological advancements, has allowed prokaryote-derived CRISPR/Cas genome-editing systems to transform our ability to manipulate, detect, image, and annotate specific DNA and RNA sequences in the living cells of diverse species. Through modern genetic engineering editing technology and high-throughput gene sequencing, we can edit and splice covalently closed circular DNA to silence it, and correct the mutation and deletion of liver cancer genes to achieve precise in situ repair of defective genes and prohibit viral infection or replication. Such manipulations do not destroy the structure of the entire genome and facilitate the cure of diseases. In this review, we discussed the possibility that CRISPR/Cas could be used as a treatment for patients with liver cancer caused by hepatitis B virus infection, and reviewed the challenges incurred by this effective gene-editing technology.

User experience (UX) has drawn the attention of the banking industry in the past few decades. Although banking systems have a complete service process to ensure financial safety for customers, the mobile banking UX has much potential to be improved. Most research in this field of study relies on existing criteria to describe a user’s experience. However, these criteria are focused more on usability measurement, which neglects to identify the requirements of end-users. Users are asked to give feedback on the provided application, limiting the scope of the user study. Therefore, this study uses mixed methods research and in-depth semi-structured interviews to collect end-user UX requirements to build a UX measurement framework of five main services transfers, including financial management, loans, account openings, and credit cards. This study uses an online survey to validate and revise the framework by applying analytic hierarchy process (AHP) analysis to quantify criteria. We interviewed 17 customers and collected 857 online validation surveys, and 400 customers attended the AHP analysis. As a result, this study proposes a three-level measurement framework for mobile banking applications in a Chinese context. The first-level criteria are scenario requirements (24.03%), data requirements (20.98%), and function requirements (54.99%). We hope that the framework will guide designers and researchers to design better user-friendly user interfaces and improve customer satisfaction rates in the future.

Background: While some contacts of COVID-19 cases become symptomatic and radiographically abnormal, their SARS-CoV-2 RNA tests remain negative throughout the disease course. This prospective population-based cohort study aimed to explore their characteristics and significances.Methods: From January 22, 2020, when the first COVID-19 case was identified in Hefei, China, until July 3, a total of 14,839 people in Feidong, Hefei, with a population of ~1,081,000 underwent SARS-CoV-2 RNA testing, where 36 cases (0.2%) with confirmed COVID-19 infection (Group 1) and 27 close contacts (0.2%) testing negative for SARS-CoV-2 RNA but having both positive COVID-19 exposure histories and CT findings (Group 2) from eight clusters were prospectively identified. Another 62 non-COVID-19 pneumonia cases without any exposure history (Group 3) were enrolled, and characteristics of the three groups were described and compared. We further described a cluster with an unusual transmission pattern.Results: Fever was more common in Group 2 than Groups 1 and 3. Frequency of diarrhea in Group 1 was higher than in Groups 2 and 3. Median leucocyte, neutrophil, monocyte, and eosinophil counts were all lower in Groups 1 and 2 than in Group 3. Median D-dimer level was lower in Group 1 than in Groups 2 and 3. Total protein and albumin levels were higher in Groups 1 and 2 than in Group 3. C-reactive protein level was lower and erythrocyte sedimentation rate slower in Groups 1 and 2 than in Group 3. Combination antibacterial therapy and levofloxacin were more often used in Group 3 than in Groups 1 and 2. Lopinavir/ritonavir was more often administered in Groups 1 and 2 than in Group 3. Group 1 received more often corticosteroids than Groups 2 and 3. Group 2 received less often oxygen therapy than Groups 1 and 3. Median duration from illness onset to discharge was longer in Group 1 (27 d) than Groups 2 and 3 (both 17 d). Among contacts of a confirmed COVID-19 patient, only one had a positive virus RNA test but remained asymptomatic and had negative CT findings, and three had negative virus RNA tests but had symptoms and positive CT findings, one of whom transmitted COVID-19 to another asymptomatic laboratory-confirmed patient who had no other exposures.Conclusions: Among close contacts of confirmed COVID-19 cases, some present with positive symptoms and CT findings but test negative for SARS-CoV-2 RNA using common respiratory (throat swab and sputum) specimens; they have features more similar to confirmed COVID-19 cases than non-COVID-19 pneumonia cases and might have transmitted SARS-CoV-2 to others. Such cases might add to the complexity and difficulty of COVID-19 control. Our hypothesis-generating study might suggest that SARS-CoV-2 RNA testing by rRT-PCR assays of common respiratory (throat swab and sputum) specimens alone, the widely accepted “golden standard” for diagnosing COVID-19, might be sometimes insufficient, and that further studies with some further procedures (e.g., testing via bronchoalveolar lavage or specific antibodies) would be warranted for Group 2-like patients, namely, the SARS-CoV-2 RNA-negative (tested using common respiratory specimens), radiographically positive, symptomatic contacts of COVID-19 cases, to further reveal their nature.

Pancreatic cancer is known for its notorious fast progression and poor prognosis. Long noncoding RNA (lncRNA) AL161431.1 has been reported to be involved in the pathogenesis of different cancers. In this study, we explored the role of lncRNA AL161431.1 in the development and progression of pancreatic cancer by bioinformatic analysis, in vitro and in vivo experiments in pancreatic cancer BxPC-3 and SW1990 cells, as well as clinical samples. We found that lncRNA AL161431.1 was highly expressed in pancreatic cancer cells and tissues. Knock down of lncRNA AL161431.1 led to increased cancer cell death and cell cycle arrest. Xenograft growth of SW1990 cells with stable knockdown of lncRNA AL161431.1 in mice was significantly slower than that of SW1990 cells with scrambled control shRNA. Finally, we showed the involvement of lncRNA AL161431.1 in pancreatic cancer was related to its promotion of epithelial mesenchymal transition process.

Abstract Background type 2 diabetes mellitus (T2DM) is a complicated disease that can affect bone health, but the change in bone biochemical markers caused by T2DM was controversial, so the aim of this study was to investigate whether there was a discrepancy in the levels of bone biochemical markers between postmenopausal women with T2DM and non-diabetic women and to explore the relationship between the level of glycosylated hemoglobin A1c (HbA1c) and bone biochemical markers in these subjects. Methods A total of 237 type 2 diabetic postmenopausal women visiting the First Affiliated Hospital of Anhui Medical University from January 2017 to October 2018 and 93 healthy postmenopausal women were retrospectively enrolled. The differences in the levels of bone biochemical markers between patients and controls were analyzed by one-way ANOVA or chi-square test. The relationship between HbA1c and bone biochemical markers was analyzed by multivariate regression, forest plot and fitted curve. Results Bone formation markers including N-MID osteocalcin and procollagen type 1 amino-terminal pro-peptide (PINP) were decreased in postmenopausal women with T2DM compared to controls (17.42 ± 9.50 vs 23.67 ± 7.58, p = 0.74 ng/ml) showed a significantly negative with HbA1c. No significant association was seen between HbA1c and other biochemical markers. Conclusions Our study found that bone formation was inhibited in postmenopausal women with T2DM, but bone resorption was not affected, and poor glycemic control was related to lower levels of bone formation, may increase the risk of bone fracture in postmenopausal women with T2DM.

Peroxidase-mediated chemokinetic therapy (CDT) can effectively resist bacteria; however, factors such as the high dosage of drugs seriously limit the antibacterial effect. Herein, CuFeS2 nanoparticles (NPs) nanozyme antibacterial system with the photothermal effect and peroxidase-like catalytic activity are proposed as a combined antibacterial agent with biosafety, high-efficiency, and broad-spectrum antibacterial ability. In addition, the as-obtained CuFeS2 NPs with a low doses of Cu+ and Fe3+ can change the permeability of bacterial cell membranes and break the antioxidant balance by consuming intracellular glutathione (GSH), which results in more conducive ROS production. Meanwhile, the photothermal heating can regulate the CuFeS2 NPs close to their optimal reaction temperature (60 °C) to release more hydroxyl radical in low concentrations of H2O2 (100 µM). The proposed CuFeS2 NPs-based antibacterial system achieve more than 99% inactivation efficiency of methicillin-resistant Staphylococcus aureus (106 CFU mL−1 MRSA), hyperspectral bacteria β-Escherichia coli (106 CFU mL−1 ESBL) and Pseudomonas aeruginosa (106 CFU mL−1 PA), even at low concentration (2 μg mL−1), which is superior to those of the conventional CuO NPs at 4 mg mL−1 reported in the literature. In vivo experiments further confirm that CuFeS2 NPs can effectively treat wounds infected by MRSA and promote the wound healing. This study demonstrates that excellent antibacterial ability and good biocompatibility make CuFeS2 NPs a potential anti-infection nanozyme with broad application prospects.

Ammonia (NH3), a significant source of hydrogen and one of the principal constituents of fertilizer, has always been a compound of great interest and importance. However, the standard Haber–Bosch process for the synthesis of ammonia requires high temperature and high pressure, so researchers have recently focused on producing ammonia from nitrogen via a green and pollution-free method by employing the electrocatalytic nitrogen reduction reaction (NRR) under mild conditions. However, compared with industrial-scale nitrogen fixation, the yield of electrocatalytically produced ammonia is currently too low, so new catalysts with better performance are sought. Two-dimensional transition metal dichalcogenides (TMDCs) are promising catalysts for nitrogen reduction, owing to their unique electronic structure, large specific surface area, and low cost. In this paper, the NRR mechanisms are discussed and recent progress in using TMDCs in artificial nitrogen fixation is critically reviewed. We also consider strategies that could improve the performance of TMDCs for nitrogen fixation, with an emphasis on interface engineering and defect engineering. Finally, the existing limitations are discussed and the prospects for obtaining catalysts with better selectivity and higher catalytic performance are considered.

Background: Previous neuroimaging studies have demonstrated brain abnormalities in patients with hepatic diseases. However, the identified liver–brain associations are largely limited to disease-affected populations, and the nature and extent of such relations in healthy subjects remain unclear. We hypothesized that serum liver function markers within a normal level would affect brain properties.Method: One hundred fifty-seven healthy young adults underwent structural, resting-state functional, and arterial spin labeling MRI scans. Gray matter volume (GMV), regional homogeneity (ReHo), and cerebral blood flow (CBF) analyses were performed to assess brain structure, function, and perfusion, respectively. Peripheral venous blood samples were collected to measure serum liver function markers. Correlation analyses were conducted to test potential associations between liver function markers and brain imaging parameters.Results: First, serum proteins showed relations to brain structure characterized by higher albumin associated with increased GMV in the parahippocampal gyrus and amygdala and lower globulin and a higher albumin/globulin ratio with increased GMV in the olfactory cortex and parahippocampal gyrus. Second, serum bilirubin was linked to brain function characterized by higher bilirubin associated with increased ReHo in the precuneus, middle cingulate gyrus, inferior parietal lobule, and supramarginal gyrus and decreased ReHo in the caudate nucleus. Third, serum alanine transaminase (ALT) was related to brain perfusion characterized by higher ALT associated with increased CBF in the superior frontal gyrus and decreased CBF in the middle occipital gyrus, angular gyrus, precuneus, and middle temporal gyrus. More importantly, we found that CBF in the superior frontal gyrus was a significant mediator of the association between serum ALT level and working memory performance.Conclusion: These findings may not only expand existing knowledge about the relationship between the liver and the brain but also have clinical implications for studying brain impairments secondary to liver diseases as well as providing potential neural targets for their diagnosis and treatment.

Background Human papillomavirus (HPV) infection rates in women vary regionally. This study analyzed HPV infection in women of different age groups in Hefei, China, performed follow-up on positive cases, and discussed infection prognoses. Methods Samples (7,222) of exfoliated cervical cells were collected in Hefei and tested with an HPV assay kit against 27 HPV genotypes. Statistical software was used to analyze the data. Results The total positive rate of infection was 17.13% (1,068 women), and the 51–60-year age group had the highest HPV infection rate (19.82%). There were statistically significant differences between rates in the 21–30 and 31–40 (P = 0.002), 21–30 and 41–50 (P = 0.0003), 21–30 and 51–60 (P = 0.00003), and 51–60 and >60 age groups (P = 0.046). High-risk infection (15.67%) and single infection (13.01%) were the main types of HPV infection. The dominant genotypes of high-risk infection were HPV 52 (2.42%), HPV 16 (2.01%), HPV 53 (1.43%), HPV 58 (1.32%) and HPV 66 (1.01%). We conducted follow-up on cases in 69 of 94 women who had a history of 1–4 years of positive infection, and in 18 (seven treated, 11 untreated) patients, infection status turned negative (26.09%). Seventeen of the fifty-one women whose infections did not turn negative received treatment. Persistent infection was predominantly observed in high-risk genotypes (56 of 69). Conclusions The results recommend that women in Hefei improve health awareness and receive a 9-valent vaccine. Additionally, women with persistent infections should consult a gynecologist to prevent cervical lesions.

Objective: To explore the diagnostic value of serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein assay in the early stages of SARS-COV-2 infection.Methods: Serum N protein level in SARS-COV-2 infected patients and non-SARS-COV-2 infected population was measured by enzyme-linked immunosorbent assay (ELISA) double antibody sandwich assay. Colloidal gold immunochromatography assay was used to detect serum N protein antibodies in the above populations.Results: Fifty cases of SARS-CoV-2 nucleic acid-positive and SARS-CoV-2 antibody-negative patients had a serum N protein positivity rate of 76%. Thirty-seven patients who were positive for serum SARS-CoV-2 antibody after infection had a serum SARS-CoV-2 N protein positivity rate of 2.7%. Serum N protein test results of 633 non-SARS-COV-2 infected patients, including pregnant women, patients with other respiratory infections, and individuals with increased rheumatoid factor were all negative, with serum N protein concentration