MICROORGANISMS FROM HANDS OF TRADITIONAL CHINESE MEDICAL DOCTORS IN A CENTRAL HOSPITAL ENVIRONMENT

Background: In a central hospital, the heavy clinical workload makes one to overlook its hazard to health and can to a large extent promote the transmission of pathogenic microorganisms. It is not uncommon however, to observe practices that deviate from normal standards of hygiene. Hand contact between doctors of TCM and patients may lead to nosocomial infections. Materials and Methods: Samples were sourced and collected from hands of TCM doctors in a central hospital. The fungal isolates were identified by colonial morphology and microscopic examination. Sensitivity test were performed on each of the identified isolates using the Multiple Disc Diffusion method. Results: A total of 265 samples were collected from the fingers, palm and back of hands of TCM doctors. Seven organisms were isolated, with S. aureus being the most common bacterium with frequency of 55.9% in the hospital environment. Other bacteria isolated included P. aeruginosa, E. coli and K. aerogenes. S. cerevisae was the most common fungus isolated with frequency of 61.8%. Fungi isolated included P. chrysogenum and A. niger. Conclusion: The study showed clearly that hand contact between TCM doctors and patients may lead to infection of exposed susceptible patients. Results of antibiotic susceptibility pattern show that isolates in this study are mostly resistant to augmentin and most antibiotics of old generation, while gentamycin and pefloxacin were highly active against most of isolates. Considering the possibility of transmission of contamination, special attention should be directed towards disinfection of TCM doctors’ hands

The Role of Toll-Like Receptors in Skin Host Defense, Psoriasis, and Atopic Dermatitis.

As the key defense molecules originally identified in Drosophila, Toll-like receptor (TLR) superfamily members play a fundamental role in detecting invading pathogens or damage and initiating the innate immune system of mammalian cells. The skin, the largest organ of the human body, protects the human body by providing a critical physical and immunological active multilayered barrier against invading pathogens and environmental factors. At the first line of defense, the skin is constantly exposed to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), and TLRs, expressed in a cell type-specific manner by various skin cells, serve as key molecules to recognize PAMPs and DAMPs and to initiate downstream innate immune host responses. While TLR-initiated inflammatory responses are necessary for pathogen clearance and tissue repair, aberrant activation of TLRs will exaggerate T cell-mediated autoimmune activation, leading to unwanted inflammation, and the development of several skin diseases, including psoriasis, atopic dermatitis, systemic lupus erythematosus, diabetic foot ulcers, fibrotic skin diseases, and skin cancers. Together, TLRs are at the interface between innate immunity and adaptive immunity. In this review, we will describe current understanding of the role of TLRs in skin defense and in the pathogenesis of psoriasis and atopic dermatitis, and we will also discuss the development and therapeutic effect of TLR-targeted therapies

Roles of a CCR4–NOT complex component GmNOT4-1 in regulating soybean nodulation

Legume-rhizobial symbiotic nitrogen fixation is the most efficient nitrogen assimilation system in the ecosystem. In the special interaction between organ–root nodules, legumes supply rhizobial carbohydrates for their proliferation, while rhizobials provide host plants with absorbable nitrogen. Nodule initiation and formation require a complex molecular dialogue between legumes and rhizobia, which involves the accurate regulation of a series of legume genes. The CCR4–NOT complex is a conserved multi-subunit complex with functions regulating gene expression in many cellular processes. However, the functions of the CCR4–NOT complex in rhizobia–host interactions remain unclear. In this study, we identified seven members of the NOT4 family in soybean and further classified them into three subgroups. Bioinformatic analysis showed that NOT4s shared relatively conserved motifs and gene structures in each subgroup, while there were significant differences between NOT4s in the different subgroups. Expression profile analysis indicated that NOT4s may be involved in nodulation in soybean, as most of them were induced by Rhizobium infection and highly expressed in nodules. We further selected GmNOT4-1 to clarify the biological function of these genes in soybean nodulation. Interestingly, we found that either GmNOT4-1 overexpression or down-regulation of GmNOT4-1 by RNAi or CRISPR/Cas9 gene editing would suppress the number of nodules in soybean. Intriguingly, alterations in the expression of GmNOT4-1 repressed the expression of genes in the Nod factor signaling pathway. This research provides new insight into the function of the CCR4–NOT family in legumes and reveals GmNOT4-1 to be a potent gene for regulating symbiotic nodulation

Integrative analysis of DNA methylomes reveals novel cell-free biomarkers in lung adenocarcinoma

Lung cancer is a leading cause of cancer-related deaths worldwide, with a low 5-year survival rate due in part to a lack of clinically useful biomarkers. Recent studies have identified DNA methylation changes as potential cancer biomarkers. The present study identified cancer-specific CpG methylation changes by comparing genome-wide methylation data of cfDNA from lung adenocarcinomas (LUAD) patients and healthy donors in the discovery cohort. A total of 725 cell-free CpGs associated with LUAD risk were identified. Then XGBoost algorithm was performed to identify seven CpGs associated with LUAD risk. In the training phase, the 7-CpGs methylation panel was established to classify two different prognostic subgroups and showed a significant association with overall survival (OS) in LUAD patients. We found that the methylation of cg02261780 was negatively correlated with the expression of its representing gene GNA11. The methylation and expression of GNA11 were significantly associated with LAUD prognosis. Based on bisulfite PCR, the methylation levels of five CpGs (cg02261780, cg09595050, cg20193802, cg15309457, and cg05726109) were further validated in tumor tissues and matched non-malignant tissues from 20 LUAD patients. Finally, validation of the seven CpGs with RRBS data of cfDNA methylation was conducted and further proved the reliability of the 7-CpGs methylation panel. In conclusion, our study identified seven novel methylation markers from cfDNA methylation data which may contribute to better prognosis for LUAD patients

Deciphering the age-dependent changes of pulmonary fibroblasts in mice by single-cell transcriptomics

Background and objectives: The heterogeneity of pulmonary fibroblasts, a critical aspect of both murine and human models under physiological and pathological conditions, is well-documented. Yet, consensus remains elusive on the subtypes, lineage, biological attributes, signal transduction pathways, and plasticity of these fibroblasts. This ambiguity significantly impedes our understanding of the fibrotic processes that transpire in lung tissue during aging. This study aims to elucidate the transcriptional profiles, differentiation pathways, and potential roles of fibroblasts within aging pulmonary tissue.Methods: We employed single-cell transcriptomic sequencing via the 10x Genomics platform. The downstream data were processed and analyzed using R packages, including Seurat. Trajectory and stemness of differentiation analyses were conducted using the Monocle2 and CytoTRACE R packages, respectively. Cell interactions were deciphered using the CellChat R package, and the formation of collagen and muscle fibers was identified through Masson and Van Geison staining techniques.Results: Our analysis captured a total of 22,826 cells, leading to the identification of fibroblasts and various immune cells. We observed a shift in fibroblasts from lipogenic and immune-competent to fibrotic and myofibroblast-like phenotype during the aging process. In the aged stage, fibroblasts exhibited a diminished capacity to express chemokines for immune cells. Experimental validation confirmed an increase of collagen and muscle fiber in the aged compared to young lung tissues. Furthermore, we showed that TGFβ treatment induced a fibrotic, immunodeficient and lipodystrophic transcriptional phenotype in young pulmonary fibroblasts.Conclusion: We present a comprehensive single-cell transcriptomic landscape of lung tissue from aging mice at various stages, revealing the differentiation trajectory of fibroblasts during aging. Our findings underscore the pivotal role of fibroblasts in the regulation of immune cells, and provide insights into why age increases the risk of pulmonary fibrosis

Deep muscularis propria tumor invasion without lymph node metastasis as a unique subclassification of stage IB gastric cancer: a retrospective study

BACKGROUND: The prognosis difference based on the depth of tumor muscularis propria invasion in gastric cancer (GC) was still debated, and therapy strategy for stage IB GC patient required further investigation. METHODS: A total of 380 patients with pT2 GC after radical surgery were retrospectively analyzed, including 185 in superficial muscularis propria (sMP) group and 195 in deep muscularis propria (dMP) group. RESULTS: The overall survival (OS) was significantly better for patients in sMP group than for patients in dMP group (P = 0.007). In multivariate analysis, depth of tumor invasion, pN stage, age, primary location, positive expression of p53, elevated maximal LDH, elevated initial CA19-9 and AFP level were independent prognostic factors for OS. The sMP group had a significantly better OS than dMP group (P = 0.014) in pN0 stage. After further stratification, the survival outcomes were not significantly different between deep muscularis propria tumor invasion without lymph node metastasis (dMPN0) group (stage IB) and superficial muscularis propria tumor invasion with stage 1-2 lymph node metastasis (sMPN1-2) group (stage II) (P = 0.100). Patients with adjuvant chemotherapy had a statistically better survival than those without in dMPN0 group (P = 0.045) and dMPN0 patients with adjuvant chemotherapy had better OS than sMPN1-2 patients (P = 0.015). In addition, greater postoperative survival could be observed in sMPN0 patients than dMPN0 patients in p53-positive group (P = 0.002), and similar OS could be seen between dMPN0 patients with p53-positive and T2N1-2 patients (P = 0.872). CONCLUSION: As a unique subclassification of stage IB GC, appropriate adjuvant chemotherapy should be considered for patients with dMPN0 stage. In addition, positive expression of p53, elevated LDH could be potential factors in identifying the different prognoses for stage IB GC patients