Improving bioelectrochemical performance by sulfur-doped titanium dioxide cooperated with Zirconium based metal-organic framework (S-TiO2@MOF-808) as cathode in microbial fuel cells.

The sulfur-doped titanium dioxide (S-TiO2) cooperated with Zirconium based on a kind of metal-organic framework (MOF-808) was successfully prepared as cathode catalyst (S-TiO2@MOF-808) of microbial fuel cell (MFC) by two-step hydrothermal reaction. The particle size was approximately 5 µm, and the spherical S-TiO2 particle was attached to the surface of MOF-808 as irregular block solid. Zr-O, C-O and O-H bond were indicated to exist in S-TiO2@MOF-808. When n (Zr4+): n(Ti4+) was 1: 5, S-TiO2@MOF-808 showed better oxygen reduction reaction (ORR). The introduction of S-TiO2 restrained the framework collapse of MOF-808, S-TiO2@MOF-808 showed much higher catalytic stability in reaction. The recombination of sulfur and TiO2 reduced the charge transfer resistance, accelerated the electron transfer rate, and improved ORR greatly. The maximum power density of S-TiO2@MOF-808-MFC was 84.05 mW/m2, about 2.17 times of S-TiO2-MFC (38.64 mW/m2). The maximum voltage of S-TiO2@MOF-808-MFC was 205 mV, and the stability was maintained for 6 d.

A multi-cycle signal amplification-mediated single quantum dot nanosensor for PIWI-interacting RNA detection.

We construct a single quantum dot-based nanosensor for piRNA detection based on ligation-mediated multi-cycle signal amplification. This nanosensor is homogenous, selective, and sensitive with a detection limit of 0.104 fM. Moreover, it can detect the endogenous piRNA level in different cell lines, and discriminate cancer tissues from normal tissues.

Dissecting molecular evolution of class 1 integron gene cassettes and identifying their bacterial hosts in suburban creeks via epicPCR.

OBJECTIVES: Our study aimed to sequence class 1 integrons in uncultured environmental bacterial cells in freshwater from suburban creeks and uncover the taxonomy of their bacterial hosts. We also aimed to characterize integron gene cassettes with altered DNA sequences relative to those from databases or literature and identify key signatures of their molecular evolution. METHODS: We applied a single-cell fusion PCR-based technique-emulsion, paired isolation and concatenation PCR (epicPCR)-to link class 1 integron gene cassette arrays to the phylogenetic markers of their bacterial hosts. The levels of streptomycin resistance conferred by the WT and altered aadA5 and aadA11 gene cassettes that encode aminoglycoside (3″) adenylyltransferases were experimentally quantified in an Escherichia coli host. RESULTS: Class 1 integron gene cassette arrays were detected in Alphaproteobacteria and Gammaproteobacteria hosts. A subset of three gene cassettes displayed signatures of molecular evolution, namely the gain of a regulatory 5'-untranslated region (5'-UTR), the loss of attC recombination sites between adjacent gene cassettes, and the invasion of a 5'-UTR by an IS element. Notably, our experimental testing of a novel variant of the aadA11 gene cassette demonstrated that gaining the observed 5'-UTR contributed to a 3-fold increase in the MIC of streptomycin relative to the ancestral reference gene cassette in E. coli. CONCLUSIONS: Dissecting the observed signatures of molecular evolution of class 1 integrons allowed us to explain their effects on antibiotic resistance phenotypes, while identifying their bacterial hosts enabled us to make better inferences on the likely origins of novel gene cassettes and IS that invade known gene cassettes.

Antibody responses to SARS-CoV-2 Omicron infection in patients with hematological malignancies: A multicenter, prospective cohort study.

Little is known about antibody responses to natural Omicron infection and the risk factors for poor responders in patients with hematological malignancies (HM). We conducted a multicenter, prospective cohort study during the latest Omicron wave in Chongqing, China, aiming to compare the antibody responses, as assessed by IgG levels of anti-receptor binding domain of spike protein (anti-S-RBD), to Omicron infection in the HM cohort (HMC) with healthy control cohort (HCC), and solid cancer cohort (SCC). In addition, we intend to explore the risk factors for poor responders in the HMC. Among the 466 HM patients in this cohort, the seroconversion rate was 92.7%, no statistically difference compared with HCC (98.2%, p = 0.0513) or SCC (100%, p = 0.1363). The median anti-S-RBD IgG titer was 29.9 ng/mL, significantly lower than that of HCC (46.9 ng/mL, p < 0.0001) or SCC (46.2 ng/mL, p < 0.0001). Risk factors associated with nonseroconversion included no COVID-19 vaccination history (odds ratio [OR] = 4.58, 95% confidence interval [CI]: 1.75-12.00, p = 0.002), clinical course of COVID-19 ≤ 7 days (OR = 2.86, 95% CI: 1.31-6.25, p = 0.008) and severe B-cell reduction (0-10/µL) (OR = 3.22, 95% CI: 1.32-7.88, p = 0.010). Risk factors associated with low anti-S-RBD IgG titer were clinical course of COVID-19 ≤ 7 days (OR = 2.58, 95% CI: 1.59-4.18, p < 0.001) and severe B-cell reduction (0-10/µL) (OR = 2.87, 95% CI: 1.57-5.24, p < 0.001). This study reveals a poor antibody responses to Omicron (BA.5.2.48) infection in HM patients and identified risk factors for poor responders. Highlights that HM patients, especially those with these risk factors, may be susceptible to SARS-CoV-2 reinfection, and the postinfection vaccination strategies for these patients should be tailored. Clinical trial: ChiCTR2300071830.

A biomimetic chip to assess subcutaneous bioavailability of monoclonal antibodies in humans.

Subcutaneous (subQ) injection is a common route for delivering biotherapeutics, wherein pharmacokinetics is largely influenced by drug transport in a complex subQ tissue microenvironment. The selection of good drug candidates with beneficial pharmacokinetics for subQ injections is currently limited by a lack of reliable testing models. To address this limitation, we report here a Subcutaneous Co-Culture Tissue-on-a-chip for Injection Simulation (SubCuTIS). SubCuTIS possesses a 3D coculture tissue architecture, and it allows facile quantitative determination of relevant scale independent drug transport rate constants. SubCuTIS captures key in vivo physiological characteristics of the subQ tissues, and it differentiates the transport behavior of various chemically distinct molecules. We supplemented the transport measurements with theoretical modeling, which identified subtle differences in the local absorption rate constants of seven clinically available mAbs. Accounting for first-order proteolytic catabolism, we established a mathematical framework to assess clinical bioavailability using the local absorption rate constants obtained from SubCuTIS. Taken together, the technology described here broadens the applicability of organs-on-chips as a standardized and easy-to-use device for quantitative analysis of subQ drug transport.

Effects of bundle-care interventions on pressure ulcers in patients with stroke: A meta-analysis.

We conducted a meta-analysis to assess the effects of bundle-care interventions on pressure ulcers in patients with stroke to provide a basis for clinical work. Randomised controlled trials on the effects of bundle-care interventions in patients with stroke were identified using computerised searches of the PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, VIP and Wanfang databases, from the time of inception of each database to July 2023, supplemented by manual literature searches. Two researchers independently retrieved and screened the articles, extracted the data and evaluated the quality of the included studies. After reaching consensus, meta-analysis was performed using RevMan 5.4. Twenty-four papers were included, involving 3330 patients of whom 1679 were in the intervention group and 1651 were in the control group. The results showed that, compared with standard care, bundle-care interventions significantly reduced the incidence of pressure ulcers (3.28% vs. 14.84%, odds ratio [OR]: 0.19, 95% confidence interval [CI]: 0.14-0.26, p < 0.001), and aspiration (5.60% vs. 18.84%, OR: 0.25, 95% CI: 0.17-0.39, p < 0.001), and improved patient satisfaction with nursing care (96.59% vs. 84.43%, OR. 5.45, 95% CI: 3.76-7.90, p < 0.001). Current evidence suggests that care bundles are significantly better than conventional nursing measures in preventing pressure ulcers and aspiration, and improving patient satisfaction with nursing care in patients with stroke, and are worthy of clinical promotion and application.

Antibody responses following the surge of SARS-CoV-2 Omicron infection among patients with systemic autoimmune rheumatic diseases.

Objectives: The surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron infections has affected most Chinese residents at the end of 2022, including a number of patients with systemic autoimmune rheumatic diseases (SARDs). Methods: To investigate the antibody level of the Omicron variant in SARD patients after SARS-CoV-2 Omicron infection, we tested BA.5.2 and BF.7 Omicron variant IgG antibody levels using ELISA on blood samples collected from 102 SARD patients and 19 healthy controls (HCs). The type of SARD, demographics, concurrent treatment, doses of SARS-CoV-2 vaccines and outcomes were also recorded. Results: A total of 102 SARD patients (mean age: 40.3 years; 89.2% female), including 60 SLE, 32 RA and 10 other SARDs, were identified. Of these, 87 (85.3%) were infected with SARS-CoV-2. We found that the BA.5.2 and BF.7 antibody levels of infected SARD patients were lower than those of HCs (P < 0.05). Sixty-five (63.7%) patients had at least one dose of a SARS-CoV-2 vaccine. SARD patients with at least two doses of SARS-CoV-2 vaccine had a higher level of BA.5.2 and BF.7 antibodies than the unvaccinated group (P < 0.05). There was no evidence for a significant inhibitory effect of glucocorticoids (GCs) on the BA.5.2 and BF.7 Omicron variant antibody levels in SARD patients. SLE patients using biologic DMARDs had a lower BA.5.2 Omicron variant antibody level than patients using GCs and/or HCQ. Conclusion: These data suggest that patients with SARDs had a lower antibody response than HCs after Omicron infection.

Identifying immune cell infiltration and effective diagnostic biomarkers in Crohn's disease by bioinformatics analysis.

Background: Crohn's disease (CD) has an increasing incidence and prevalence worldwide. It is currently believed that both the onset and progression of the disease are closely related to immune system imbalance and the infiltration of immune cells. The aim of this study was to investigate the molecular immune mechanisms associated with CD and its fibrosis through bioinformatics analysis. Methods: Three datasets from the Gene Expression Omnibus data base (GEO) were downloaded for data analysis and validation. Single sample gene enrichment analysis (ssGSEA) was used to evaluate the infiltration of immune cells in CD samples. Immune cell types with significant differences were identified by Wilcoxon test and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Differentially expressed genes (DEGs) were screened and then subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional correlation analysis, as well as protein-protein interaction (PPI) network analysis. The cytoHubba program and the GSE75214 dataset were used to screen for hub genes and plot Receiver operating characteristic (ROC)curves to screen for possible biomarkers of CD based on diagnostic efficacy. The hub genes of CD were correlated with five significantly different immune cells. In addition, validation was performed by real time quantitative PCR (RT-qPCR) experiments in colonic tissue of CD intestinal fibrosis rats to further identify hub genes that are more related to CD intestinal fibrosis. Results: The DEGs were analyzed separately by 10 algorithms and narrowed down to 9 DEGs after taking the intersection. 4 hub genes were further screened by the GSE75214 validation set, namely COL1A1, CXCL10, MMP2 and FGF2. COL1A1 has the highest specificity and sensitivity for the diagnosis of CD and is considered to have the potential to diagnose CD. Five immune cells with significant differences were screened between CD and health controls (HC). Through the correlation analysis between five kinds of immune cells and four biomarkers, it was found that CXCL10 was positively correlated with activated dendritic cells, effector memory CD8+ T cells. MMP2 was positively correlated with activated dendritic cells, gamma delta T cells (γδ T) and mast cells. MMP2 and COL1A1 were significantly increased in colon tissue of CD fibrosis rats. Conclusion: MMP2, COL1A1, CXCL10 and FGF2 can be used as hub genes for CD. Among them, COL1A1 can be used as a biomarker for the diagnosis of CD. MMP2 and CXCL10 may be involved in the development and progression of CD by regulating activated dendritic cell, effector memory CD8+ T cell, γδ T cell and mast cell. In addition, MMP2 and COL1A1 may be more closely related to CD intestinal fibrosis.

A Streamlined Approach for Fluorescence Labelling of Low-Copy-Number Plasmids for Determination of Conjugation Frequency by Flow Cytometry.

Bacterial conjugation plays a major role in the dissemination of antibiotic resistance and virulence traits through horizontal transfer of plasmids. Robust measurement of conjugation frequency of plasmids between bacterial strains and species is therefore important for understanding the transfer dynamics and epidemiology of conjugative plasmids. In this study, we present a streamlined experimental approach for fluorescence labelling of low-copy-number conjugative plasmids that allows plasmid transfer frequency during filter mating to be measured by flow cytometry. A blue fluorescent protein gene is inserted into a conjugative plasmid of interest using a simple homologous recombineering procedure. A small non-conjugative plasmid, which carries a red fluorescent protein gene with a toxin-antitoxin system that functions as a plasmid stability module, is used to label the recipient bacterial strain. This offers the dual advantage of circumventing chromosomal modifications of recipient strains and ensuring that the red fluorescent protein gene-bearing plasmid can be stably maintained in recipient cells in an antibiotic-free environment during conjugation. A strong constitutive promoter allows the two fluorescent protein genes to be strongly and constitutively expressed from the plasmids, thus allowing flow cytometers to clearly distinguish between donor, recipient, and transconjugant populations in a conjugation mix for monitoring conjugation frequencies more precisely over time.

Urine-derived mesenchymal stem cells-derived exosomes enhances survival and proliferation of aging retinal ganglion cells.

OBJECTIVES: This study was designed to investigate to test the effect of exosomes from urine-derived mesenchymal stem cells (USCs) on the survival and viability of aging retinal ganglion cells (RGCs), and explored the preliminary related mechanisms. METHODS: Primary USCs were cultured and identified by immunofluorescence staining. Aging RGCs models were established by D-galactose treatment and identified by ß-Galactosidase staining. After treatment with USCs conditioned medium (with USCs removal), flow cytometry was performed to examine the apoptosis and cell cycle of RGCs. Cell viability of RGCs was detected by Cell-counting Kit 8 (CCK8) assay. Moreover, gene sequencing and bioinformatics analysis were applied to analyze the genetic variation after medium treatment in RGCs along with the biological functions of differentially expressed genes (DEGs). RESULTS: The number of apoptotic aging RGCs was significantly reduced in USCs medium-treated RGCs. Besides, USCs-derived exosomes exert significant promotion on the cell viability and proliferation of aging RGCs. Further, sequencing data analyzed and identified DEGs expressed in aging RGCs and aging RGCs treated with USCs conditioned medium. The sequencing outcomes demonstrated 117 upregulated genes and 186 downregulated genes in normal RGCs group vs aging RGCs group, 137 upregulated ones and 517 downregulated ones in aging RGCs group vs aging RGCs + USCs medium group. These DEGs involves in numerous positive molecular activities to promote the recovery of RGCs function. CONCLUSIONS: Collectively, the therapeutic potentials of USCs-derived exosomes include suppression on cell apoptosis, enhancement on cell viability and proliferation of aging RGCs. The underlying mechanism involves multiple genetic variation and changes of transduction signaling pathways.

Cellular Localization and Distribution of TGF-ß1, GDNF and PDGF-BB in the Adult Primate Central Nervous System.

The available data on the localization of transforming growth factor beta1 (TGF-ß1), glial cell line-derived neurotrophic factor (GDNF), and platelet-derived growth factor-BB (PDGF-BB) in the adult primate and human central nervous system (CNS) are limited and lack comprehensive and systematic information. This study aimed to investigate the cellular localization and distribution of TGF-ß1, GDNF, and PDGF-BB in the CNS of adult rhesus macaque (Macaca mulatta). Seven adult rhesus macaques were included in the study. The protein levels of TGF-ß1, PDGF-BB, and GDNF in the cerebral cortex, cerebellum, hippocampus, and spinal cord were analyzed by western blotting. The expression and location of TGF-ß1, PDGF-BB, and GDNF in the brain and spinal cord was examined by immunohistochemistry and immunofluorescence staining, respectively. The mRNA expression of TGF-ß1, PDGF-BB, and GDNF was detected by in situ hybridization. The molecular weight of TGF-ß1, PDGF-BB, and GDNF in the homogenate of spinal cord was 25 KDa, 30 KDa, and 34 KDa, respectively. Immunolabeling revealed GDNF was ubiquitously distributed in the cerebral cortex, hippocampal formation, basal nuclei, thalamus, hypothalamus, brainstem, cerebellum, and spinal cord. TGF-ß1 was least distributed and found only in the medulla oblongata and spinal cord, and PDGF-BB expression was also limited and present only in the brainstem and spinal cord. Besides, TGF-ß1, PDGF-BB, and GDNF were localized in the astrocytes and microglia of spinal cord and hippocampus, and their expression was mainly found in the cytoplasm and primary dendrites. The mRNA of TGF-ß1, PDGF-BB, and GDNF was localized to neuronal subpopulations in the spinal cord and cerebellum. These findings suggest that TGF-ß1, GDNF and PDGF-BB may be associated with neuronal survival, neural regeneration and functional recovery in the CNS of adult rhesus macaques, providing the potential insights into the development or refinement of therapies based on these factors.

Uncovering Bacterial Hosts of Class 1 Integrons in an Urban Coastal Aquatic Environment with a Single-Cell Fusion-Polymerase Chain Reaction Technology.

Horizontal gene transfer (HGT) is a key driver of bacterial evolution via transmission of genetic materials across taxa. Class 1 integrons are genetic elements that correlate strongly with anthropogenic pollution and contribute to the spread of antimicrobial resistance (AMR) genes via HGT. Despite their significance to human health, there is a shortage of robust, culture-free surveillance technologies for identifying uncultivated environmental taxa that harbor class 1 integrons. We developed a modified version of epicPCR (emulsion, paired isolation, and concatenation polymerase chain reaction (PCR)) that links class 1 integrons amplified from single bacterial cells to taxonomic markers from the same cells in emulsified aqueous droplets. Using this single-cell genomic approach and Nanopore sequencing, we successfully assigned class 1 integron gene cassette arrays containing mostly AMR genes to their hosts in coastal water samples that were affected by pollution. Our work presents the first application of epicPCR for targeting variable, multigene loci of interest. We also identified the Rhizobacter genus as novel hosts of class 1 integrons. These findings establish epicPCR as a powerful tool for linking taxa to class 1 integrons in environmental bacterial communities and offer the potential to direct mitigation efforts toward hotspots of class 1 integron-mediated dissemination of AMR.

Identification of integrons and gene cassette-associated recombination sites in bacteriophage genomes.

Bacteriophages are versatile mobile genetic elements that play key roles in driving the evolution of their bacterial hosts through horizontal gene transfer. Phages co-evolve with their bacterial hosts and have plastic genomes with extensive mosaicism. In this study, we present bioinformatic and experimental evidence that temperate and virulent (lytic) phages carry integrons, including integron-integrase genes, attC/attI recombination sites and gene cassettes. Integrons are normally found in Bacteria, where they capture, express and re-arrange mobile gene cassettes via integron-integrase activity. We demonstrate experimentally that a panel of attC sites carried in virulent phage can be recognized by the bacterial class 1 integron-integrase (IntI1) and then integrated into the paradigmatic attI1 recombination site using an attC x attI recombination assay. With an increasing number of phage genomes projected to become available, more phage-associated integrons and their components will likely be identified in the future. The discovery of integron components in bacteriophages establishes a new route for lateral transfer of these elements and their cargo genes between bacterial host cells.

Differential diagnosis of gallbladder neoplastic polyps and cholesterol polyps with radiomics of dual modal ultrasound: a pilot study.

PURPOSE: To verify whether radiomics techniques based on dual-modality ultrasound consisting of B-mode and superb microvascular imaging (SMI) can improve the accuracy of the differentiation between gallbladder neoplastic polyps and cholesterol polyps. METHODS: A total of 100 patients with 100 pathologically proven gallbladder polypoid lesions were enrolled in this retrospective study. Radiomics features on B-mode ultrasound and SMI of each lesion were extracted. Support vector machine was used to classify adenomas and cholesterol polyps of gallbladder for B-mode, SMI and dual-modality ultrasound, respectively, and the classification results were compared among the three groups. RESULTS: Six, eight and nine features were extracted for each lesion at B-mode ultrasound, SMI and dual-modality ultrasound, respectively. In dual-modality ultrasound model, the area under the receiver operating characteristic curve (AUC), classification accuracy, sensitivity, specificity, and Youden's index were 0.850 ± 0.090, 0.828 ± 0.097, 0.892 ± 0.144, 0.803 ± 0.149 and 0.695 ± 0.157, respectively. The AUC and Youden's index of the dual-modality model were higher than those of the B-mode model (p < 0.05). The AUC, accuracy, specificity and Youden's index of the dual-modality model were higher than those of the SMI model (p < 0.05). CONCLUSIONS: Radiomics analysis of the dual-modality ultrasound composed of B-mode and SMI can improve the accuracy of classification between gallbladder neoplastic polyps and cholesterol polyps.

Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor.

OBJECTIVE: This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn's disease (CD) regulated by moxibustion through bile acid (BA) enterohepatic circulation and intestinal farnesoid X receptor (FXR). METHODS: Sprague-Dawley rats were randomly divided into control group, CD model group, mild moxibustion group and herb-partitioned moxibustion group. CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu (ST25) and Qihai (CV6). The changes in CD symptoms were rated according to the disease activity index score, the serum and colon tissues of rats were collected, and the pathological changes in colon tissues were observed via histopathology. Western blot, immunohistochemistry (IHC) and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway. RESULTS: Mild moxibustion and herb-partitioned moxibustion improved the symptoms of CD, inhibited inflammation and repaired mucosal damage to the colon in CD rats. Meanwhile, moxibustion could improve the abnormal expression of BA in the colon, liver and serum, downregulate the expression of interferon-γ and upregulate the expression of FXR mRNA, and inhibit Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA. The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression. Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR. Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-κB p65. In particular, herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon. CONCLUSION: Mild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA, activating colonic FXR, regulating the TLR4/MyD88 pathway, inhibiting intestinal inflammation and repairing the intestinal mucosal barrier. Herb-partitioned moxibustion seems to have more advantages in regulating BA enterohepatic circulation and FXR activation. Please cite this article as: Shen JC, Qi Q, Han D, Lu Y, Huang R, Zhu Y, Zhang LS, Qin XD, Zhang F, Wu HG, Liu HR. Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor. J Integr Med. 2023; 21(2): 194-204.

An MPA-based optimized grey Bernoulli model for China's petroleum consumption forecasting.

The remarkable prediction of petroleum consumption is of significance for energy scheduling and economic development. Considering the uncertainty and volatility of petroleum system, this paper presents a nonlinear grey Bernoulli model with combined fractional accumulated generation operator to forecast China's petroleum consumption and terminal consumption. The newly designed model introduces a combined fractional accumulated generation operator by incorporating the traditional fractional accumulation and conformable fractional accumulation; compared to the old accumulation, the newly optimized accumulation can enhance flexible ability to excavate the development patterns of time-series. In addition, to further improve the prediction performance of the new model, marine predation algorithm is applied to determine the optimal emerging coefficients such as fractional accumulation order. Furthermore, the proposed model is verified by a numerical example of coal consumption; and this newly established model is applied to predict China's petroleum consumption and terminal consumption. Our tests suggest that the designed ONGBM(1,1,k,c) model outperforms the other benchmark models. Finally, we predict China's petroleum consumption in the following years with the aid of the optimized model. According to the forecasts of this paper, some suggestions are provided for policy-makers in the relevant sectors.

Diagnostic Study of Multi-spectral Intelligent Analyzer in Diagnosis of the Infiltration Degree of Lung Adenocarcinoma / 中国肺癌杂志

BACKGROUND@#Lung cancer is one of the most common malignant tumors in the world. The accuracy of intraoperative frozen section (FS) in the diagnosis of lung adenocarcinoma infiltration cannot fully meet the clinical needs. The aim of this study is to explore the possibility of improving the diagnostic efficiency of FS in lung adenocarcinoma by using the original multi-spectral intelligent analyzer.@*METHODS@#Patients with pulmonary nodules who underwent surgery in the Department of Thoracic Surgery, Beijing Friendship Hospital, Capital Medical University from January 2021 to December 2022 were included in the study. The multispectral information of pulmonary nodule tissues and surrounding normal tissues were collected. A neural network model was established and the accuracy of the neural network diagnostic model was verified clinically.@*RESULTS@#A total of 223 samples were collected in this study, 156 samples of primary lung adenocarcinoma were finally included, and a total of 1,560 sets of multispectral data were collected. The area under the curve (AUC) of spectral diagnosis in the test set (10% of the first 116 cases) of the neural network model was 0.955 (95%CI: 0.909-1.000, P<0.05), and the diagnostic accuracy was 95.69%. In the clinical validation group (the last 40 cases), the accuracy of spectral diagnosis and FS diagnosis were both 67.50% (27/40), and the AUC of the combination of the two was 0.949 (95%CI: 0.878-1.000, P<0.05), and the accuracy was 95.00% (38/40).@*CONCLUSIONS@#The accuracy of the original multi-spectral intelligent analyzer in the diagnosis of lung invasive adenocarcinoma and non-invasive adenocarcinoma is equivalent to that of FS. The application of the original multi-spectral intelligent analyzer in the diagnosis of FS can improve the diagnostic accuracy and reduce the complexity of intraoperative lung cancer surgery plan.
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Clinical Characteristics and Survival Analysis of Patients with Plasma Cell Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics, therapeutic response and prognosis of patients with plasma cell leukemia (PCL) and improve the understanding of this disease.@*METHODS@#The clinical manifestations, laboratory tests and treatment response of 27 patients with plasma cell leukemia treated in The Second Hospital of Shanxi Medical University from December 2010 to August 2019 were analyzed retrospectively, and their clinical characteristics were summarized. Kaplan-Meier method was used for survival analysis.@*RESULTS@#There were 18 cases of primary plasma cell leukemia (pPCL) and 9 cases of secondary plasma cell leukemia (sPCL). The male to female ratio was 1.7∶1. The median age was 62 years old. The first manifestations were bone pain, fatigue, fever, splenomegaly and bleeding, and a large number of plasma cell infiltration was observed in the morphological examination of peripheral blood and bone marrow cells. 13 cases were detected by immunotyping and all of them expressed CD38/CD138. 8 cases underwent karyotype analysis, and 3 cases were normal, clonal abnormalities occurred in 5 cases. FISH detection was performed in 12 cases, of which 8 cases were abnormal. In 17 cases of bortezomib based chemotherapy, the ovevall response rate was 52.9%, which was higher than that in the non-bortezomib group, but there was no significant difference between the two groups (P =0.242). The overall median survival time of 27 patients was 6.4 months, the median progression-free survival time was 3.5 months, and the median survival time of patients with pPCL and sPCL was 8.2 months and 2.4 months, respectively, the difference between the two groups was statistically significant (P =0.031).@*CONCLUSION@#PCL is highly invasive and has diverse clinical manifestations, and is not sensitive to traditional chemotherapy. The median survival time of patients with pPCL is relatively longer than that of patients with sPCL. The chemotherapy regimen based on bortezomib improves the treatment effectiveness and prolongs the survival time of PCL patients.

Exploring the material basis of genipin-induced hepatotoxicity in vitro / 药学学报

The current study explored the hepatotoxicity among closed-ring genipin, open-ring tautomer of genipin and gardenia blue that generated from genipin and amino acid reaction using HepaRG cells to identify the material basis of genipin-induced hepatotoxicity in vitro. The effects of temperature, pH value and different kinds of amino acids on the chemical structure tautomerism between closed-ring and open-ring tautomer of genipin and the production of gardenia blue were investigated firstly, which aimed to explicit the conditions that could distinguish the closed-ring genipin and its open-ring tautomer, and the conditions generating gardenia blue, which were applied to prepare different kinds of gardenia blue; the CCK-8 kit was employed to analyze the hepatotoxicity of closed-ring genipin, open-ring tautomer of genipin and gardenia blue. From the results, it was found that, the structure transformation from close-ring to open-ring of genipin could be inhibited under the condition with acid environment; being essential groups to generate gardenia blue, the primary amino group and the open-ring tautomer of genipin reacting to generate the dihydropyridine ring was probably the key structure of gardenia blue; the structure characteristics existed apparent distinction at the reactive temperature of 37 ℃ and 80 ℃; compared to the culture condition with pH = 7.4, the concentration of genipin with close-ring in culture medium was significantly increased at pH = 5, but the cell viability did not decreased; the cell toxicity of gardenia blue was apparently lower than open-ring tautomer of genipin, and even some kinds of gardenia blue showed growth promoting effect on HepaRG cells. Here, it was suggested potentially that open-ring tautomer of genipin be the important material basis to induce hepatotoxicity, which could provide a cue and lay a foundation for the elucidation of the underlying mechanism of genipin-induced hepatotoxicity.

NSUN5 promotes progression and predicts poor prognosis in hepatocellular carcinoma.

The 5-methylcytosine (m5C) RNA methyltransferase NOP2/Sun RNA methyltransferase 5 (NSUN5) has been reported to serve important roles in numerous diseases. However, the functions and clinical significance of NSUN5 in hepatocellular carcinoma (HCC) remain unknown. Clinical information and NSUN5 mRNA sequencing data for 374 patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database, and NSUN5 mRNA and protein expression levels in 120 patients with HCC (present study cohorts) were assessed using reverse transcription-quantitative PCR, western blotting or immunohistochemistry. The association between NSUN5 mRNA and protein expression levels and the clinical characteristics (or prognosis) of patients with HCC was analyzed using the χ2 or log-rank test. The functions of NSUN5 in HCC were evaluated using in vitro and in vivo experiments, and the mechanism by which NSUN5 affected the progression of HCC was assessed using bioinformatics analysis using LinkedOmics. NSUN5 was significantly upregulated and predicted poor prognosis in HCC according to data from both TCGA database and present study cohorts. NSUN5 significantly promoted HCC proliferation and migration in vitro and significantly induced HCC tumor growth in vivo. Bioinformatics analysis demonstrated that NSUN5 was positively correlated with genes associated with translation in HCC. It was hypothesized that overexpression of NSUN5 strengthened ribosome functions and global protein translation, which may promote the proliferation and migration of HCC. In conclusion, NSUN5 may promote the progression of HCC by enhancing translation, thus making it a potential target for HCC treatment.