The Burkholderia cepacia complex (Bcc) comprises a group of genetically related yet phenotypically diverse Gram-negative opportunistic pathogens. These organisms demonstrate significant pathogenicity in immunocompromised populations, particularly cystic fibrosis (CF) and chronic granulomatous disease (CGD) patients, causing severe infections including pneumonia, bacteremia, and urinary tract infections. Notably, Bcc infection in CF patients may progress to acute respiratory failure or the life-threatening "cepacia syndrome". Of particular concern is the widespread nosocomial colonization by Bcc strains coupled with their sophisticated multidrug resistance mechanisms, which contribute substantially to clinical treatment failures. This review systematically examines the epidemiological characteristics, clinical manifestations and resistance mechanisms of Bcc. The review aims to provide evidence-based references for improving accurate diagnosis and enhancing infection control measures against this challenging pathogen.

In the field of dental aesthetics,digital aesthetic design plays a crucial role in helping dentists to predict treatment outcomes vis-ually,as well as in enhancing the consistency of knowledge and understanding of aesthetic goals between dentists and patients.It serves as the foundation for achieving ideal aesthetic effects.However,there is no clear standard for this digital process currently in China and abroad.Many dentists lack of systematic understanding of how to carry out digital aesthetic design for treatment.To establish standardized processes for dental aesthetic design and to improve the homogeneity of treatment outcomes,Chinese Society of Digital Dental Industry(CSD-DI)convened domestic experts in related field to compile this consensus.This article elaborates on the key aspects of digital aesthetic data collection,integration steps,and the digital aesthetic design process.It also formulates a decision tree for dental aesthetics at macro level and outlines corresponding workflows for various clinical scenarios,serving as a reference for clinicians.

Objective: To investigate the effects of 3-phosphoinositide-dependent protein kinase-1(PDK1) on the purkinje cells(PCs) in aging mice. Methods: The footprint test, elevated beam-walk test and rotarod test were used to measure the gait traits, motor balance and motor coordination of mice. Immunoflourescence was used to detect the structure of the cerebellum and the morphology of cells in the cerebellum. The expression level of PDK1, protein kinase C gamma(PKCγ) and protein kinase B(also known as AKT) and the phosphorylation of ribosomal protein S6(rpS6) in the cerebellum were detected by Western blot. Results: The mice showed motor defects in the overlap between forelimb and hindlimb, motor balance and motor coordination ability in an age-dependent manner. Furthermore, the cerebellum and the soma size of the PCs decreased in an age-dependent manner. However, the density of the PCs was not affected by age. Additionally, the expression level of the PDK1, PKCγ, AKT and the phosphorylation of rpS6 in the cerebellum were reduced with age. Conclusion The cerebellar size and the cell soma size of PCs decrease in the old mice. These effects may contribute to the reduction of the expression of PKCγ and AKT and the phosphorylation of rpS6 in the old mice, ultimately affecting the cerebellar motor coordination.

Objective:To screen prognostic genes as indicators for predicting immunoactive in tumor microenvironment(TME)of gastric cancer(GC).Methods:Paraffin tissue specimens and corresponding paracancer tissues were collected from 55 patients with GC.Total 976 GC transcriptome RNA-Seqs and clinical datasets were obtained from TCGA and GEO databases.Infiltra-tion status of immune cells and Immune/Stormal scores were calculated using the ESTIMATE and CIBERSORT algorithm.R package"limma"was performed to selected differentially expressed genes(DEGs).Univariate Cox regression analysis was used to determine prognostic factors of DEGs.qRT-PCR was demonstrated to detect mRNA expression of the hub genes.Potential biological functions of GREM1 were investigated by GSEA.Correlations of GREM1 with immune signature molecules and drug susceptibility were investigated by TISIDB and CellMiner database.Results:Immune Score was positively correlated with improved outcomes of GC patients.A total of 40 shared TME-related DEGs were selected in the high and low groups of Immune Score and Stromal Score.Four survival-related DEGs were obtained by Cox analysis,which were GREM1,SFRP2,CYP1B1 and MGP.By comparing the difference of gene expres-sion in tumor and adjacent tissues and the degree of affinity with immune microenvironment,it was found that GREM1 was most likely to play a role in immune remodeling in TME;expression of GREM1 was positively correlated with clinicopathological features(TNM),while negatively correlated with survival time of GC patients.GSEA results showed that GREM1 high-expression group were mainly enriched in immune-related active genomes.Besides,GREM1 expression was positively correlated to M2 macrophages,while negatively correlated to CD8+T cells.GREM1 was also positively associated with immunosuppressor TGF-β1,immunopotentiator ENT-PD1,chemokine CCL14 as well as receptor CCR2.Moreover,GC patients with high expression of GREM1 might more sensitive to drug Vismodegib therapy.Conclusion:GREM1 can regard as an immunosuppressive clinical indicator in TME of GC.

Humans ; Cytomegalovirus ; Cytomegalovirus Infections ; Antigens, Viral ; Immunity ; Autoimmune Diseases ; CD8-Positive T-Lymphocytes

Background:Celiac disease is an autoimmune enteropathy which can present with patchy mucosal lesions.Therefore,the diagnosis of the disease requires histological evaluation of multiple site biopsies.Aims:To analyze the pathological characteristics of multiple site small intestinal biopsies in adult patients with celiac disease and provide reference for early identification and diagnosis of celiac disease.Methods:The pathological data of 22 adult patients who were newly diagnosed as having celiac disease at the People's Hospital of Xinjiang Uygur Autonomous Region from August 2019 to April 2022 were collected retrospectively.All patients were positive for serum anti-tissue transglutaminase antibody IgA,and biopsies of duodenal bulb,descending part of the duodenum and terminal ileum were obtained under endoscopy.Histological examination was performed by experienced pathologists according to the modified Marsh grading system.Results:The most common pathological grade of duodenal bulb(50.0%)and descending part of the duodenum(45.5%)was Marsh Ⅲc,while those of terminal ileum was Marsh Ⅲa(63.6%).All of the bulb biopsies,95.5%of the descending part and 72.7%of the terminal ileum biopsies showed characteristic histological changes of celiac disease.Mucosal pathology was patchy in 7 patients,of which one patient was duodenal bulb and terminal ileum involved,and 6 were duodenum involved only.Fifteen patients had diffuse small intestinal mucosal pathology involving duodenal bulb,descending part and terminal ileum,of which 4 patients showed concordant histology(the same Marsh grade in duodenal bulb,descending part and terminal ileum)and 11 patients showed discordant histology.In 18 patients(81.8%),duodenum was the only affected site or duodenum showed more serious mucosal lesions compared with terminal ileum.Conclusions:Adult celiac disease may affect the whole small intestine,and the mucosal involvement may be patchy,which highlights the importance of taking small intestinal biopsies from multiple sites repeatedly in the diagnostic work-up of celiac disease.

OBJECTIVES: To investigate the effect of oral microscope-assisted surface decontamination on implants in vitro. METHODS: Twelve implants that fell off because of severe peri-implantitis were collected, and decontamination was carried out on the surfaces of implants through curetting, ultrasound, titanium brushing, and sandblasting at 1×, 8×, or 12.8× magnifications. The number and sizes of residues on the implants' surfaces after decontamination were determined, and the decontamination effect was analyzed according to the thread spacing in the different parts of the thread. RESULTS: 1) The 8× and 12.8× groups scored lower for implant surface residues than the 1× group (P<0.000 1), and the 12.8× group scored lower than the 8× group (P<0.001); 2) no difference in residue score was found between the wide and narrow thread pitch (P>0.05), and the 8× and 12.8× groups had lower scores than the 1× group (P<0.001); 3) the lowest number of contaminants was observed at the tip of the thread, whereas the highest was observed below the thread, and the difference was significant (P<0.001). However, the thread pitch had no effect on the number of contaminants in different areas (P>0.05); 4) the residue scores of the 8× and 12.8× groups were lower than those of the 1× group at the thread tip and above, sag, and below the thread of the implants (P<0.05). CONCLUSIONS Residues on the surfaces of contaminated implants can be effectively removed by using an oral microscope. After decontamination, the residues of pollutants were mainly concentrated below the thread of the implants, and the thread pitch of the implants had no significant effect on the residues.
Humans ; Dental Implants ; Decontamination ; Surface Properties ; Peri-Implantitis ; Titanium

Objective To explore the biological exposure limit of blood system damage caused by long-term exposure to polycyclic aromatic hydrocarbons (PAHs) in non-occupational population by using the benchmark dose method, and to provide relevant reference for further improving the assessment of PAHs-induced health damage effects. Methods Adult residents living in downwind direction of a coke-oven plant in Shanxi Province were selected as the research subjects, and the information collected from baseline was used as the control. The metabolites of PAHs in urine were used as exposure biomarker, and the abnormal rate of red blood cell index was used as response biomarker. The relationship between urinary OH-PAHs and the erythrocyte damage rate was analyzed, and the benchmark dose (BMD) and the lower confidence limitation for the benchmark dose (BMDL) were calculated using Bayesian dose-optimizing software. Results The urinary PAH metabolites were mainly naphthalene and fluorene. The detection concentrations of 2-OHFlu and 1-OHPhe in the final year were higher than those in the baseline (P<0.05). With the increase of exposure years, the abnormal rate of red blood cells in the final year was higher than that in the baseline (P<0.05). In addition, the abnormal rate of red blood cells increased with the increase of the concentrations of five metabolites of PAHs in urine, and the chi-square trend test was significant (P<0.05). The benchmark dose (BMD) of OH-PAHs was 0.67 μmol/mol Cr, 0.82 μmol/mol Cr, 1.40 μmol/mol Cr and 0.78 μmol/mol Cr, respectively. The BMD of 2-OHNap in people with barbecue diet habits was 0.23 μmol/mol Cr. The BMD of 2-OHNap in people without barbecue diet habits was 1.44 μmol/mol Cr. Conclusion There is a dose-response relationship between the concentration of PAHs metabolites in urine and the damage of red blood cells. Long-term exposure to PAHs can lead to hematological damage. It is suggested that targeted public health interventions should be formulated to reduce the exposure of the general population to PAHs.

Objective:This study is to understand the hot spots and trends in the recruitment of clinical trial subjects in China over the past 20 years, explore the existing problems and countermeasures, and provide scientific ideas for domestic clinical trial institutions to effectively solve the problem of subject recruitment.Methods:Bibliometric analysis was used to study the relevant literature from three major domestic databases from 2001 to 2021, analyzing key indicators such as annual publication volume, journal distribution, institutional distribution, regional distribution, and high-frequency keyword co-occurrence.Results:A total of 162 articles were selected. The results showed that the overall publication volume in this field showed an upward trend, and the research institutions were diversified, with a concentration of medical and pharmaceutical institutions and universities. The current research hotspots in this field focused on quality and efficiency improvement of subject recruitment, with themes of subject protection, ethical review, regulation development, standardized management, etc.Conclusions:The research in this field has made significant progress, but the overall research level is still relatively weak. Therefore, it is suggested that the country should play a role in macro-regulation, on the one hand, starting with top-level design, promoting the construction of a standardized management system for subject recruitment, continuously strengthening subject protection, and enhancing the effectiveness of scientific recruitment. On the other hand, releasing the potential of grassroots institutions and giving full play to the volume advantage by promoting the sinking of advantageous resources. Meanwhile, great importance should be attached to the development of Phase I clinical trials, giving full play to the strong internal energy of traditional medicine and promoting the development of Chinese traditional medicine. These multi-measures should provide a theoretical basis for exploring the transformation of ′clinical research hospitals′, and promote the high-quality development of new drug research and development in China.

Objective:To investigate the relationship between serum leukocyte-associated immunoglobulin-like receptor 2 (LAIR2) expression and cellular immune function, prognosis in patients with non-small cell lung cancer.Methods:From April 2016 to April 2017, 90 patients with non-small cell lung cancer who were treated in Shangqiu first people’s Hospital were taken as the lung cancer group, and they were grouped into the survival group and the death group according to whether the patients died within 5 years. Another 84 patients with benign pulmonary mass were selected as the control group. The levels of CD4+[ (28.26±5.14) % vs (47.02±6.73) %], CD8+ [ (23.76±5.84) % vs (30.12±6.03) %] and CD4+/CD8+ [ (1.17±0.30) % vs (1.56±0.50) %] in peripheral blood immune cells were detected by flow cytometry; the serum LAIR2 level was detected by enzyme-linked immunosorbent assay (ELISA) , and the average serum LAIR2 level of patients with non-small cell lung cancer was applied as the boundary, and they were grouped into a low LAIR2 expression group and a LAIR2 high expression group; Pearson correlation was applied to analyze the correlation between serum LAIR2 level and immune cell level in patients with non-small cell lung cancer; Kaplan-Meier curve was applied to analyze the relationship between serum LAIR2 level and 5-year survival rate of patients with non-small cell lung cancer; and multivariate COX regression analysis was applied to analyze the factors affecting 5-year mortality in patients with non-small cell lung cancer.Results:The level of serum LAIR2 [ (69.55±13.12) ng/ml vs. (20.64±7.13) ng/ml] in the lung cancer group was significantly higher than that in the control group, and the levels of CD4 +, CD8 + and CD4+/CD8+ were significantly lower than those in the control group ( P<0.05) . The serum LAIR2 level in patients with TNM stage III+IV (77.32±13.09) ng/ml, poorly differentiated tissue (78.14±13.26) ng/ml, and lymph node metastasis (79.02±13.81) ng/ml was significantly higher than that in patients with TNM stage I+II (64.37±12.89) ng/ml, medium/well differentiated tissue (64.32±12.73) ng/ml, and no lymph node metastasis (62.92±12.85) ng/ml ( P<0.05) . The levels of CD4 +, CD8 + and CD4 +/CD8 + in the LAIR2 high expression group were significantly lower than those in the LAIR2 low expression group ( P<0.05) . Serum LAIR2 level in patients with non-small cell lung cancer was negatively correlated with CD4+, CD8+ and CD4+/CD8+ levels ( r=-0.510, -0.496, -0.494, P<0.05) . The 5-year survival rate of patients with high LAIR2 expression was lower than that of patients with low LAIR2 expression ( r=6.375, P<0.05) . LAIR2 was an independent risk factor for 5-year death in patients with non-small cell lung cancer ( P<0.05) . Conclusion:LAIR2 is highly expressed in serum of patients with non-small cell lung cancer, and its expression level is closely related to cellular immune function and prognosis.