Lymph node metastases are strongly associated with unfavorable prognosis in papillary thyroid carcinoma (PTC) patients. However, there are few sensitive or specific indicators that can diagnose or ...predict lymph node metastases in PTC. The objective of our study was to identify reliable indicators for the diagnosis and prediction of lymph node metastases of PTC. The PTC data set was obtained from The Cancer Genome Atlas (TCGA) cohort. Information on tumor-infiltrating immune cells in PTC was acquired using single-sample gene set enrichment analysis (ssGSEA). Then, the progression-free survival (PFS) rates of PTC patients were evaluated by Kaplan–Meier curves. A tissue microarray including 58 normal thyroid tissues and 57 PTC tissues was processed for CD19 immunohistochemistry staining. Finally, evaluation of phenotype permutations was performed using gene set enrichment analysis (GSEA). There was an appreciable association between immune infiltration and lymph node metastases in PTC. Among those immune cells, B cells and cytotoxic cells showed significant predictive accuracy for lymph node metastases in PTC. Tumor-infiltrating B cells and NK cells were associated with favorable prognosis, while tumor-associated NK CD56
bright
cells were correlated with poor prognosis in PTC patients. IHC analyses of PTC further confirmed a notably negative correlation between B cell infiltration and lymph node metastases in PTC. Additionally, mutations in BRAF, a dominant cause of tumor mutation burden (TMB), were positively correlated with reduced B cell infiltration and lymph node metastases in PTC. GSEA revealed that epithelial-mesenchymal transition, IL-6/JAK/STAT3 signaling, the inflammatory response, and TNF-α signaling via the NFκB pathway were remarkably suppressed pathways in patients with BRAF mutations. Tumor-associated lymphocytic infiltration, especially B cell infiltration, provides diagnostic and prognostic value for lymph node metastases in PTC.
Background/Aims: As an “ESKAPE” pathogen, Acinetobacter baumannii is one of the leading causes of drug-resistant infections in humans. Phage therapy may be a useful strategy in treating infections ...caused by drug-resistant A. baumannii. Among 21 phage strains that were isolated and described earlier, we investigated the therapeutic efficacy of Abp1 because of its relatively wide host range. Methods: Phage stability assays were used to evaluate thermal and pH stability of Abp1. Abp1 was co-cultured with A. baumannii (AB1) over a range of multiplicities of infection to determine its bactericidal efficacy. HeLa or THP-1 cells were used in the cytotoxicity and protection assays. Finally, the therapeutic effects of Abp1 on local and systemic A. baumannii infection in mice were determined. Results: We found that Abp1 exhibits high thermal and pH stability and has a low frequency of lysogeny. Bacteriophage resistance also occurs at a very low frequency (3.51±0.46×10-8), and Abp1 can lyse almost all host cells at a MOI as low as 0.1. Abp1 has no detectable cytotoxicity to HeLa or THP-1 cells as determined by LDH release assay. Abp1 can rescue HeLa cells from A. baumannii infection, even if introduced 2 hours post infection. In both local and systemic A. baumannii infection mouse models, Abp1 treatment exhibits good therapeutic effects. Conclusion: Abp1 is an excellent candidate for phage therapy against drug-resistant A. baumannii infections.
Background and objectives
Accurate identification and evaluation of the parathyroid glands (PGs) intraoperatively is critical to reduce the incidence of postoperative hypoparathyroidism after total ...thyroidectomy. Near-infrared fluorescence imaging (NIFI), including the autofluorescence (AF) and indocyanine green fluorescence (ICGF) imaging, is a promising technique to protect PGs. This study aimed to assess whether the combined use of AF and ICGF could reduce the incidence of postoperative hypoparathyroidism and improve the identification and evaluation of PGs during total thyroidectomy.
Methods
This randomized controlled trial enrolled 180 patients who were randomized into two groups and underwent total thyroidectomy with unilateral or bilateral central lymph node dissection. In the control group, the PGs were identified and evaluated by the naked eye. In the NIFI group, AF was used to identify the PGs and ICGF was applied to assess the blood perfusion of the PGs
in situ
. The primary outcome was the incidence of postoperative hypoparathyroidism. The secondary outcomes included the number of identified PGs, autotransplanted PGs, and known preserved PGs
in situ
.
Results
The incidence of postoperative transient hypoparathyroidism was significantly lower in the NIFI group than in the control group (27.8% vs. 43.3%,
P
= 0.029). More PGs were identified in the NIFI group than in the control group (3.6 ± 0.5 vs. 3.2 ± 0.4,
P
< 0.001). No significant difference was observed in the number of autotransplanted PGs between the two groups (
P
= 0.134). Compared with the control group, a greater number of known PGs were preserved
in situ
in the NIFI group (1.3 ± 0.6 vs. 1.0 ± 0.5,
P
< 0.001). In the NIFI group, only 4.5% of the patients with at least one well-perfused PG (ICG score of 2) developed postoperative hypoparathyroidism, which was significantly lower than that of the control group (34.6%,
P
< 0.001).
Conclusion
Combined use of AF and ICGF during total thyroidectomy reduces the risk of transient postoperative hypoparathyroidism, enhances the ability to identify and preserve PGs, and improves the accuracy of evaluating the perfusion of PGs during surgery.
Clinical Trial Registration
Chinese Clinical Trial Register (
www.chictr.org.cn
), identifier ChiCTR2100045320. Registered on April 12, 2021.
Acinetobacter baumannii is a growing threat, although lytic bacteriophages have been shown to effectively kill A. baumannii. However, the interaction between the host and the phage has not been fully ...studied. We demonstrate the global profile of transcriptional changes in extensively drug-resistant A. baumannii AB1 and the interaction with phage φAbp1 through RNA sequencing (RNA-seq) and bioinformatic analysis. Only 15.6% (600/3,838) of the genes of the infected host were determined to be differentially expressed genes (DEGs), indicating that only a small part of the bacterial resources was needed for φAbp1 propagation. Contrary to previous similar studies, more upregulated rather than downregulated DEGs were detected. Specifically, φAbp1 infection caused the most extensive impact on host gene expression at 10 min, which was related to the intracellular accumulation phase of virus multiplication. Based on the gene coexpression network, a middle gene (
, encoding phage-associated RNA polymerase) showed a negative interaction with numerous host ribosome protein genes. In addition, the gene expression of bacterial virulence/resistance factors was proven to change significantly. This work provides new insights into the interactions of φAbp1 and its host, which contributes to the further understanding of phage therapy, and provides another reference for antibacterial agents.
Previous research has reported the transcriptomic phage-host interactions in Escherichia coli and Pseudomonas aeruginosa, leading to the detailed discovery of transcriptomic regulations and predictions of specific gene functions. However, a direct relationship between A. baumannii and its phage has not been previously reported, although A. baumannii is becoming a rigorous drug-resistant threat. We analyzed transcriptomic changes after φAbp1 infected its host, extensively drug-resistant (XDR) A. baumannii AB1, and found defense-like responses of the host, step-by-step control by the invader, elaborate interactions between host and phage, and elevated drug resistance gene expressions of AB1 after phage infection. These findings suggest the detailed interactions of A. baumannii and its phage, which may provide both encouraging suggestions for drug design and advice for the clinical use of vital phage particles.
is the leading cause of infection in burn patients. The increasing carbapenem resistance of
has become a serious challenge to clinicians. The present study investigated the molecular typing and ...carbapenem resistance mechanisms of 196
isolates from the bloodstream and wound surface of patients in our burn center over a period of 6 years. By multilocus sequence typing (MLST), a total of 58 sequence types (STs) were identified. An outbreak of ST111, a type that poses a high international risk, occurred in 2014. The isolates from wound samples of patients without bacteremia were more diverse and more susceptible to antibiotics than strains collected from the bloodstream or the wound surface of patients with bacteremia. Importantly, a large proportion of the patients with multisite infection (46.51%) were simultaneously infected by different STs in the bloodstream and wound surface. Antimicrobial susceptibility testing of these isolates revealed high levels of resistance to carbapenems, with 35.71% susceptibility to imipenem and 32.14% to meropenem. To evaluate mechanisms associated with carbapenem resistance, experiments were conducted to determine the prevalence of carbapenemase genes, detect alterations of the
porin gene, and measure expression of the
β-lactamase gene and the
multidrug efflux gene. The main mechanism associated with carbapenem resistance was mutational inactivation of
(88.65%), accompanied by overexpression of
(68.09%). In some cases,
was inactivated by insertion sequence element IS
, which has not been found previously in
. These findings may help control nosocomial
infections and improve clinical practice.
Summary
Streptococcus suis has emerged as a causative agent of human meningitis and streptococcal toxic shock syndrome over the last years. The high pathogenicity of S. suis may be due in part to a ...laterally acquired pathogenicity island (renamed SsPI‐1), which can spontaneously excise and transfer to recipients. Cells harboring excised SsPI‐1 can potentially lose this island if cell division occurs prior to its reintegration; however, attempts to cure SsPI‐1 from the host cells have been unsuccessful. Here, we report that an SsPI‐1‐borne Epsilon/Zeta toxin–antitoxin system (designated SezAT) promotes SsPI‐1 stability in bacterial populations. The sezAT locus consists of two closely linked sezT and sezA genes encoding a toxin and its cognate antitoxin, respectively. Overproduction of SezT induces a bactericidal effect that can be neutralized by co‐expression of SezA, but not by its later action. When devoid of a functional SezAT system, large‐scale deletion of SsPI‐1 is straightforward. Thus, SezAT serves to ensure inheritance of SsPI‐1 during cell division, which may explain the persistence of epidemic S. suis. This report presents the first functional characterization of TA loci in S. suis, and the first biochemical evidence for the adaptive significance of the Epsilon/Zeta system in the evolution of pathogen virulence.
Streptococcus suis is a re‐emerging pathogen capable of causing human meningitis and streptococcal toxic shock syndrome, which may be due to a laterally acquired pathogenicity island (renamed SsPI‐1). SsPI‐1 can spontaneously excise to form an extrachromosomal circular product, however, attempts to cure SsPI‐1 have been unsuccessful. Here, we report that a functional Epsilon/Zeta toxin‐antitoxin system promotes SsPI‐1 stability in bacterial populations, which may explain the persistence of epidemic S. suis.
Introduction
Postoperative hypoparathyroidism (POH) is the most common and important complication for thyroid cancer patients who undergo total thyroidectomy. Intraoperative parathyroid ...autotransplantation has been demonstrated to be essential in maintaining functional parathyroid tissue, and it has clinical significance in identifying essential factors of serum parathyroid hormone (PTH) levels for patients with parathyroid autotransplantation. This retrospective cohort study aimed to comprehensively investigate influential factors in the occurrence and restoration of POH for patients who underwent total thyroidectomy with intraoperative parathyroid autotransplantation (TTIPA).
Method
This study was conducted in a tertiary referral hospital, with a total of 525 patients who underwent TTIPA. The postoperative serum PTH levels were collected after six months, and demographic characteristics, clinical features and associated operative information were analyzed.
Results
A total of 66.48% (349/525) of patients who underwent TTIPA were diagnosed with POH. Multivariate logistic regression indicated that Hashimoto’s thyroiditis (OR=1.93, 95% CI: 1.09-3.42), P=0.024), the number of transplanted parathyroid glands (OR=2.70, 95% CI: 1.91-3.83, P<0.001) and postoperative blood glucose levels (OR=1.36, 95% CI: 1.06-1.74, P=0.016) were risk factors for POH, and endoscopic surgery (OR=0.39, 95% CI: 0.22-0.68, P=0.001) was a protective factor for POH. Multivariate Cox regression indicated that PTG autotransplantation patients with same-side central lymph node dissection (CLND) (HR=0.50; 95% CI: 0.34-0.73, P<0.001) demonstrated a longer time for increases PTH, and female patients (HR=1.35, 95% CI: 1.00-1.81, P=0.047) were more prone to PTH increases. Additionally, PTG autotransplantation with same-side CLND (HR=0.56, 95% CI: 0.38-0.82, P=0.003) patients had a longer time to PTH restoration, and patients with endoscopic surgery (HR=1.54, 95% CI: 1.04-2.28, P=0.029) were more likely to recover within six months.
Conclusion
High postoperative fasting blood glucose levels, a large number of transplanted PTGs, open surgery and Hashimoto’s thyroiditis are risk factors for postoperative POH in TTIPA patients. Elevated PTH levels occur earlier in female patients and patients without CLND on the transplant side. PTH returns to normal earlier in patients without CLND and endoscopic surgery on the transplant side.
The gastrointestinal microbiome is crucial in human health. With greater than 10 times the cell count of an individual, the gastrointestinal microbiome provides many benefits to the host. It plays an ...important role in chronic illnesses and immune diseases and also following burns and trauma. This study aimed to determine whether severe burns affect the gastrointestinal microbiome during the early stages of after burn injury and the extent to which the microbiome is disturbed by such burns. We used a rat burn model to investigate any changes occurring in the microbiome after the burn trauma using 16S rRNA sequencing and downstream α-diversity, β-diversity, and taxonomy analysis. With 128631 and 143694 clean sequence reads, an average of 2287 and 2416 operational taxonomic units (OTUs) were recognized before and after the burn injury, respectively. Bacterial diversity within the pre- and post-burn groups was similar according to OTU richness, Chao 1 index, Shannon index and ACE index. However, the constituents of the gastrointestinal microbiota changed after the burn injury. Compared with the pre-burn samples, the post-burn samples showed a tendency to cluster together. The ratio of Firmicutes to Bacteroidetes decreased after the burn injury. Also, the abundance of some probiotic organisms (i.e., butyrate-producing bacteria and Lactobacillus) decreased after the burn injury. In contrast, opportunistic pathogenic bacteria, such as those of the genera
and
and the phylum of Proteobacteria are more abundant post-burn. In conclusion, dysbiosis in the gastrointestinal microbiome was observed after the burn injury. Although the total number of species in the gastrointestinal microbiome did not differ significantly between the pre- and post-burn injury groups, the abundance of some bacterial components was affected to various extents.
is a common pathogen isolated from burn patients that can form biofilms on burn wounds and implanted deep vein catheters, which often leads to refractory infections or even biofilm-related sepsis. As ...biofilm formation is usually regulated by environmental conditions, we hypothesized that serum composition may be altered after burn injury, potentially affecting the ability of infecting bacteria to form biofilms. As predicted, we observed that serum from burn-injured rats increases biofilm formation by
and also induces bacterial aggregation and adherence to human fibronectin and fibrinogen. Analysis of potential regulatory factors revealed that exposure to burn serum decreases expression of the quorum-sensing
system and increases mRNA levels of some biofilm inducers such as
and
. In addition, we also observed that burn serum imposes oxidative stress and increases expression of key oxidoreductase genes (
,
,
, and
) in
. Importantly, the ability of burn serum to enhance biofilm formation and bacterial cell aggregation can be abrogated by treatment with an antioxidant. Taken together, these findings indicate that burn serum increases
biofilm formation via elevated oxidative stress, and may lead to novel strategies to control biofilm formation and infection in burn patients.
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