Objective:
Nasopharyngeal carcinoma is highly endemic in Southeast China. Circulating tumor cell is an important biomarker in the prognosis of variety kinds of cancers. Overexpression of fibronectin ...1 was observed in variety kinds of malignancies and may contribute to progress and metastasis of the cancers. The current study was aimed to investigate phenotypes of circulating tumor cell in nasopharyngeal carcinoma blood and fibronectin 1 expression in the circulating tumor cell, and their clinical application in predicting nasopharyngeal carcinoma prognosis.
Methods:
Blood samples were obtained from nasopharyngeal carcinoma patients before and after treatment. CanPatrol circulating tumor cell enrichment and RNA in situ hybridization were applied to identify circulating tumor cell and its phenotypes. Fibronectin 1 messenger RNA expression in the cells of circulating tumors was examined by messenger RNA-in situ hybridization.
Results:
Circulating tumor cell was not associated with tumor characteristics or lymph node metastasis. Patients with >9 circulating tumor cells or >5 mesenchymal phenotype circulating tumor cell per 5-mL blood had poorer progression-free survival (P < .05). Multivariable analysis demonstrated that 2 or more mesenchymal phenotype circulating tumor cells with high fibronectin 1 messenger RNA expression predicted shorter progression-free survival (P < .05).
Conclusions:
Circulating tumor cells with high-level fibronectin 1 expression was associated with poor survival in patients with nasopharyngeal carcinoma and could be an independent prognostic factor for nasopharyngeal carcinoma.
Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is an aggressive entity within the World Health Organization classification of lymphoid tumors. The International Prognostic Index is ...reported to be prognostically meaningful for ENKTL, but lacks discriminatory power for stage I/II ENKTL with extensive local invasion. This study aimed to evaluate the prognostic effects of local invasion by site and tissue type in patients with ENKTL.
We retrospectively analyzed data of 86 patients who were diagnosed with ENKTL by the Department of Pathology of Beijing Tongren Hospital from June 2002 to April 2016, and ascertained tumor infiltration of adjacent structures (AS), bone, and soft tissue for each patient, using physical findings and imaging scans. We used univariate and multivariate analysis to assess the association of each involved tissue or site with patients' overall survival (OS).
Of the 86 patients, 71 (82.6%) experienced invasion of AS, 22 (25.6%) of soft tissue, and 26 (30.2%) had bone involvement. Overall, patients with AS involvement did not show significantly shorter survival than those without AS involvement (Log rank χ = 1.177, P = 0.278); however, patients who had involved eyeballs or brains showed significantly lower 2-year OS rates than those without eyeball involvement (Log rank χ = 4.105, P = 0.043) or brain involvement (Log rank χ = 7.126, P = 0.008). Patients with involved local soft tissue or bones, respectively, showed lower 2-year OS rates than those without involved local soft tissue (Log rank χ = 10.390, P = 0.001) or bones (Log rank χ = 8.993, P = 0.003). Multivariate analysis showed that involvement of the cheek or facial muscles (hazard ratio, HR = 5.471, 95% confidence interval CI: 1.466-20.416, P = 0.011) and the maxilla bone (HR = 6.120, 95% CI: 1.517-24.694, P = 0.011) were significantly independent predictors of lower 2-year OS rates.
Imaging can accurately detect ENKTL invasion of AS, soft tissue, and bone. Involvement of local soft tissue or bone was significantly associated with lower 2-year OS rates. Involvements of the cheek or facial muscle, as well as maxilla bone, are independent predictors of lower 2-year OS rates in ENKTL patients.
Patients undergoing hemodialysis (HD) are particularly vulnerable to coronavirus disease 2019 (COVID-19) and are at increased risk of developing severe infection. However, given the exclusion of such ...patients from clinical trials, there are limited data regarding the effectiveness of the antiviral drug nirmatrelvir/ritonavir (N/R) in patients on HD. We prescribed N/R to 4 patients on HD with COVID-19 after obtaining informed consent. Their clinical symptoms were improved at approximately 3 days after N/R administration. The viral load was reduced after approximately 10 days. The main adverse effects were nausea and vomiting. Rational dosage adjustment obtained good tolerance but did not influence the efficacy. These results suggest that N/R may be a promising agent for patients on HD with COVID-19.
Background
The optimal surgical management of patients with incidental gallbladder cancer (IGBC) and their long-term survival remains unclear.
Objective
The purpose of this study was to examine the ...long-term prognosis of patients with IGBC diagnosed during or after LC.
Methods
Between January 2002 and January 2012, a total of 7,582 consecutive patients underwent LC for presumed gallbladder benign disease in the Chinese PLA General Hospital, China. Among them, 69 patients (0.91 %) were diagnosed to have IGBC. Their medical records, imaging data, surgery records, pathological findings, and survival data were retrospectively reviewed.
Results
Median age was 61 years (range: 34–83). After a median follow-up period of 61 months, the 1-, 3-, and 5-year survival rates of patients were 89.9, 78.3, and 76.8 %, respectively. The 5-year survival rates of patients with T1a, T1b, T2, and T3 stages were 95.5, 93.8, 69.2, and 44.4 %, respectively. The 5-year survival rates in simple LC (
n
= 45), converted to open extended cholecystectomy (
n
= 16), and radical second resection (
n
= 8) groups were 91.1, 37.5, and 75.0 %, respectively. Local port-site tumor recurrence was identified in one patient. Prognostic factors including depth of invasion, lymph node status, vascular or neural invasion, tumor differentiation, extent of resection, bile spillage, and type of surgery were statistically significant (
p
< 0.05).
Conclusions
Simple LC is appropriate for T1a patients with clear margin and unbroken gallbladder, whereas extended radical resection is recommended for patients with T1b or more advanced IGBC. An intact surgical specimen and the use of plastic retrieval bags are important to reduce the risk of port-site recurrences and disease relapse. Early diagnosis, meticulous perioperative assessment, and precise surgery are essential factors to obtain good results in IGBC treatment.
: The pathophysiological mechanisms underlying postoperative cognitive dysfunction (POCD) remain unclear over the years. Neuroinflammation caused by surgery has been recognized as an important ...element in the development of POCD. Many studies also suggest that the vagus nerve plays an important role in transmitting peripheral injury signals to the central nervous system (CNS) and the resultant neuroinflammation. Previously, we have demonstrated that brain mast cells (BMCs), as the "first responders", play a vital role in neuroinflammation and POCD. However, how the vagus nerve communicates with BMCs in POCD has not yet been clarified.
: In the current study, we highlighted the role of the vagus nerve as a conduction highway in surgery-induced neuroinflammation for the first time. In our model, we tested if mice underwent unilateral cervical vagotomy (VGX) had less neuroinflammation compared to the shams after laparotomy (LP) at an early stage. To further investigate the roles of mast cells and glutamate in the process, we employed Kit
mice and primary bone marrow-derived MCs to verify the glutamate-NR2B axis on MCs once again.
: Our results demonstrated that there were higher levels of glutamate and BMCs activation as early as 4 h after LP. Meanwhile, vagotomy could partially block the increases and reduce neuroinflammation caused by peripheral inflammation during the acute phase. Excitingly, inhibition of NR2B receptor and knockout of mast cells can attenuateneuroinflammation induced by glutamate.
: Taken together, our findings indicate that the vagus is a high-speed pathway in the transmission of peripheral inflammation to the CNS. Activation of BMCs triggered a neuroinflammatory cascade. Inhibition of NR2B receptor on BMCs can reduce glutamate-induced BMCs activation, neuroinflammation, and memory impairment, suggesting a novel treatment strategy for POCD.
Objectives
We aimed at investigating whether serum exosomal miR‐16‐5p could be utilized as an immunotherapy biomarker in lung adenocarcinoma (LUAD) patients administered by programmed cell death ...ligand‐1 (PD‐L1) inhibitors, and to evaluate its functions in LUAD progression.
Methods
Sixty LUAD sufferers and 20 healthy controls (HCs) were covered in this work. We applied both IHC and WB to examine PD‐L1 level in clinical tissue samples and utilized WB to quantify PD‐L1 expression in LUAD cells and LUAD xenograft tissues, respectively. Transmission electron microscopy (TEM), WB, and nanoparticle tracking analysis (NTA) were executed to confirm the exosomes isolated from serum specimens and cell culture media. To quantify of exosomal miR‐16‐5p level from serum and culture medium of cultured cell, qRT‐PCR experiment was utilized. The connection between tissue PD‐L1 level and serum exosomal miR‐16‐5p expression in PD‐L1‐positive sufferers administered by PD‐L1 inhibitors was verified using Spearman correlation coefficient analysis. In addition, the overall survival (OS) and progression‐free survival (PFS) rates among PD‐L1 inhibitor managed sufferers were acquired through a follow‐up visit. Finally, we used a group of assays, including 5‐bromo‐2′‐dexoyuridine (BrdU) and colony formation test, wound healing experiment, flow cytometry, and nude mice xenograft experiment, to explore the functions of circulating exosomal miR‐16‐5p on LUAD cell proliferation, apoptosis, and migration, as well as tumor development, respectively.
Results
PD‐L1 expression was positively related to T stage (tumor size stage), and PD‐L1 inhibitor treatment reduced the PD‐L1 expression and mitigated T stage in PD‐L1‐positive LUAD sufferers. For PD‐L1‐positive LUAD sufferers, elevated PD‐L1 expression or reduced serum exosomal miR‐16‐5p level were linked to longer PFS and OS upon PD‐L1 inhibitor treatment. The number of exosomes in patient's serum was more than that in the serum of healthy individuals, and PD‐L1 inhibitor treatment decreased the number of serum‐derived exosomes in PD‐L1‐positive LUAD sufferers. Exosome‐derived miR‐16‐5p was downregulated in patient's serum and cell culture medium, and this was negatively linked to tumor stage and PD‐L1 expression. Meanwhile, PD‐L1 inhibitor treatment could increase the serum exosomal miR‐16‐5p expression, and the expression change of serum exosomal miR‐16‐5p was diametrically related to PD‐L1 after the treatment. Moreover, the overexpression of PD‐L1 accelerated tumor growth and decreased the exosomal miR‐16‐5p content in cell culture media, while exosomal miR‐16‐5p overexpression in cell culture media inhibited tumor development by decreasing the PD‐L1 expression. Exosomal miR‐16‐5p overexpression in cell culture media also depressed LUAD cell proliferation and migration, and stimulated cell apoptosis, especially in the cells which cultured in the mediums with PD‐L1 inhibitor in vitro.
Conclusions
Serum exosomal miR‐16‐5p may be a latent tumor inhibitor and a new biomarker for PD‐L1 inhibitor‐dependent immunotherapy in LUAD by regulating the PD‐L1 expression.
1.Exosomal miR‐16‐5p was downregulated in human LUAD serum samples and cell culture media. 2.Serum exosomal miR‐16‐5p was related to the tumor size stage and PD‐L1expression of LUAD patients. 3.Overexpression of exosomal miR‐16‐5p repressed cell proliferation and migration, stimulate cell apoptosis, and restrain tumor growth by lowering the PD‐L1 expression.
Time to detection experiments (TTD) based on turbidometry using an automatic Bioscreen C is a useful and straightforward method for estimating microbial growth parameters (lag time (λ), growth rate ...(μ) and “work to be done” (h0)) at constant temperature. This study investigated the effects of slightly acidic electrolyzed water (SAEW) and heat treatment on Listeria monocytogenes growth at different recovery temperatures (10 °C, 15 °C, 25 °C, and 30 °C). Similar surviving and sublethally injured L. monocytogenes populations were obtained by heat treatment (55 °C for 10 min) and SAEW treatment (available chlorine concentration of 30 mg/l and ratio of bacteria against SAEW of 8:2 for 30 s). In these experimental conditions, stresses had greater impact on the λ and h0 parameter in comparison with recovery temperature while there was no great change in growth rate under isothermal conditions. Larger λ values and h0 parameters were observed in sublethal-heat injured L. monocytogenes (the maximum λ and h0 parameters are 30.199 h and 1.6492) as compared to SAEW groups (the maximum λ and h0 parameters are 22.634 h and 1.4396). The sensitivity analysis of SAEW and heat treatments on h0 parameter indicated that SAEW treatment showed a higher influence. The collinearity diagnostics of independent variables recovery temperature (T), μ, λ for dependent variable (h0 parameter) demonstrated that T, μ and λ had strong collinearity. In addition, the established secondary models in this study have good performances on predicting the effect of recovery temperature on bacterial growth parameters.
•Growth parameters (λ, μ, h0) of sublethal Listeria monocytogenes were measured.•The effect of recovery temperature was more pronounced than stress.•Stresses only have marked impact on the lag time of cells.•Secondly models of recovery temperature and growth parameters were developed.
Friction stir lap welding (FSLW) is expected to join the hybrid structure of aluminum alloy and steel. In this study, the Al-Mg-Si aluminum alloy and 301L stainless steel were diffusion bonded by ...FSLDW with the addition of 0.1 mm thick pure Zn interlayer, when the tool pin did not penetrate the upper aluminum sheet. The characteristics of lap interface and mechanical properties of the joint were analyzed. Under the addition of Zn interlayer, the diffusion layer structure at lap interface changed from continuous to uneven and segmented. The components of the diffusion layer were more complex, including Fe-Al intermetallic compounds (IMCs), Fe-Zn IMCs and Al-Zn eutectic. The largely changed composition and thickness of uneven and segmented diffusion layer at the lap interface played a significant role in the joint strength. The tensile shear load of Zn-added joint was 6.26 kN, increasing by 41.3% than that of Zn-not-added joint. These two joints exhibited interfacial shear fracture, while the Zn interlayer enhanced the strength of diffusion bonding by extending the propagation path of cracks.
We previously demonstrated that endothelial microparticles (EMPs) are increased in mitral valve diseases and impair valvular endothelial cell function. Perioperative systemic inflammation is an ...important risk factor and complication of cardiac surgery. In this study, we investigate whether EMPs increase in congenital heart diseases to promote inflammation and endothelial dysfunction.
The level of plasma EMPs in 20 patients with atrial septal defect (ASD), 23 patients with ventricular septal defect (VSD), and 30 healthy subjects were analyzed by flow cytometry. EMPs generated from human umbilical vascular endothelial cells (HUVECs) were injected into C57BL6 mice, or cultured with HUVECs without or with siRNAs targeting P38 MAPK. The expression and/or phosphorylation of endothelial nitric oxide synthase (eNOS), P38 MAPK, and caveolin-1 in mouse heart and/or in cultured HUVECs were determined. We evaluated generation of nitric oxide (NO) in mouse hearts, and levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cultured HUVECs and in mice.
EMPs were significantly elevated in patients with ASD and VSD, especially in those with pulmonary hypertension when compared with controls. EMPs increased caveolin-1 expression and P38 MAPK phosphorylation and decreased eNOS phosphorylation and NO production in mouse hearts. EMPs stimulated P38 MAPK expression, TNF-α and IL-6 production, which were all inhibited by siRNAs targeting P38 MAPK in cultured HUVECs.
EMPs were increased in adult patients with congenital heart diseases and may contribute to increased inflammation leading to endothelial dysfunction via P38 MAPK-dependent pathways. This novel data provides a potential therapeutic target to address important complications of surgery of congenial heart disease.
The association between mucosal microbiota and HIV-1 infection has garnered great attention in the field of HIV-1 research. Previously, we reported a receptor-independent HIV-1 entry into epithelial ...cells mediated by a Gram-negative invasive bacterium, Porphyromonas gingivalis. Here, we present evidence showing that P. gingivalis outer membrane vesicles (OMVs) promote mucosal transmission of HIV-1. We demonstrated, using the Dynabeads technology, a specific interaction between HIV-1 and P. gingivalis OMVs which led to an OMV-dependent viral entry into oral epithelial cells. HIV-1 was detected in human oral keratinocytes (HOKs) after a 20 minute exposure to the HIV-vesicle complexes. After entry, most of the complexes appeared to dissociate, HIV-1 was reverse-transcribed, and viral DNA was integrated into the genome of HOKs. Meanwhile, some of the complexes exited the original host and re-entered neighboring HOKs and permissive cells of HIV-1. Moreover, P. gingivalis vesicles enhanced HIV-1 infection of MT4 cells at low infecting doses that are not able to establish an efficient infection alone. These findings suggest that invasive bacteria and their OMVs with ability to interact with HIV-1 may serve as a vehicle to translocate HIV through the mucosa, establish mucosal transmission of HIV-1, and enhance HIV-1 infectivity.
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