The chest X-ray score baseline in predicting continuous oxygen therapy failure in low-risk aged patients after thoracic surgery.

Background: Radiographic severity assessment can be instrumental in diagnosing postoperative pulmonary complications (PPCs) and guiding oxygen therapy. The radiographic assessment of lung edema (RALE) and Brixia scores correlate with disease severity, but research on low-risk elderly patients is lacking. This study aimed to assess the efficacy of two chest X-ray scores in predicting continuous oxygen therapy (COT) treatment failure in patients over 70 years of age after thoracic surgery. Methods: From January 2019 to December 2021, we searched for patients aged 70 years and above who underwent thoracic surgery and received COT treatment, with a focus on those at low risk of respiratory complications. Bedside chest X-rays, RALE, Brixia scores, and patient data were collected. Univariate, multivariate analyses, and 1:2 matching identified risk factors. Receiver operating characteristic (ROC) curves determined score sensitivity, specificity, and predictive values. Results: Among the 242 patients surviving to discharge, 19 (7.9%) patients experienced COT failure. COT failure correlated with esophageal cancer surgeries, thoracotomies (36.8% vs. 9%, P=0.003; 26.3% vs. 9.4%, P=0.004), and longer operation time (3.4 vs. 2.8 h, P=0.003). Surgical approach and RALE score were independent risk factors. The prediction model had an area under the curve (AUC) of 0.839 [95% confidence interval (CI), 0.740-0.938]. Brixia and RALE scores predicted COT failure with AUCs of 0.764 (95% CI, 0.650-0.878) with a cut-off value of 6.027 and 0.710 (95% CI, 0.588-0.832) with a cut-off value of 17.134, respectively, after 1:2 matching. Conclusions: The RALE score predict the risk of COT failure in elderly, low-risk thoracic patients better than the Brixia score. This simple, cheap, and noninvasive method helps evaluate postoperative lung damage, monitor treatment response, and provide early warning for oxygen therapy escalation. Further studies are required to confirm the validity and applicability of this model in different settings and populations.

Granzyme A Produced by γ9δ2 T Cells Activates ER Stress Responses and ATP Production, and Protects Against Intracellular Mycobacterial Replication Independent of Enzymatic Activity.

Mycobacterium tuberculosis (Mtb), the pathological agent that causes tuberculosis (TB) is the number one infectious killer worldwide with one fourth of the world's population currently infected. Data indicate that γ9δ2 T cells secrete Granzyme A (GzmA) in the extracellular space triggering the infected monocyte to inhibit growth of intracellular mycobacteria. Accordingly, deletion of GZMA from γ9δ2 T cells reverses their inhibitory capacity. Through mechanistic studies, GzmA's action was investigated in monocytes from human PBMCs. The use of recombinant human GzmA expressed in a mammalian system induced inhibition of intracellular mycobacteria to the same degree as previous human native protein findings. Our data indicate that: 1) GzmA is internalized within mycobacteria-infected cells, suggesting that GzmA uptake could prevent infection and 2) that the active site is not required to inhibit intracellular replication. Global proteomic analysis demonstrated that the ER stress response and ATP producing proteins were upregulated after GzmA treatment, and these proteins abundancies were confirmed by examining their expression in an independent set of patient samples. Our data suggest that immunotherapeutic host interventions of these pathways may contribute to better control of the current TB epidemic.

Contrast-Enhanced Ultrasound in Locating Axillary Sentinel Lymph Nodes in Patients with Breast Cancer: A Prospective Study.

The objective was to explore the clinical value of contrast-enhanced ultrasound (CEUS) in locating the sentinel lymph node (SLN) in patients with early breast cancer. We screened 143 consecutive patients with breast cancer between July 2017 and August 2019. The number of SLNs identified by CEUS and dual labeling (blue dye and radiolabeled colloid) were recorded. The accuracy of CEUS plus fine-needle aspiration cytology (FNAC) was assessed. The rate of identification of SLNs with CEUS was 84.0% (121/144), and that of dual labeling was 97.92% (141/144). There was no significant association between non-enhancement (p = 0.060) or inhomogeneous enhancement (p = 0.468) and lymph node metastasis. The sensitivity and specificity of CEUS-SLNs plus FNAC was 78.38% and 100%, respectively. The technique of CEUS is a promising method for locating the axillary SLN. But it is hard to identify lymph node metastasis with CEUS alone. CEUS-SLNs plus FNAC is a sound technique for diagnosis of the metastasis of SLN.

A postoperative comparison of high-flow nasal cannula therapy and conventional oxygen therapy for esophageal cancer patients.

BACKGROUND: Hypoxaemia in post-surgical patients of esophageal cancer (EC) is common in thoracic departments. However, few studies have investigated the role of high-flow nasal cannula (HFNC) compared with conventional oxygen therapy (COT). METHODS: A retrospective study was implemented to enroll hypoxemic patients after esophagectomy who were treated by HFNC or COT immediately after extubation between January 2019 and December 2019. We compared the effect of HFNC or COT in patients regarding the vital signs and arterial blood gases, the incidence of anastomotic leakage, postoperative pulmonary complications (PPCs), sore throat/nose, and reintubation, length of stay, and sputum production. We also 3D reconstructed the postoperative chest CT, and compared the amount of lung volume loss caused by PPCs (pneumothorax, atelectasis, pulmonary consolidation and pleural effusion) between the two groups. RESULTS: Compared to patients in COT group, sore throat/nose in HFNC group was lower, the sputum production was higher, and the total hospital stay was shorter. Compared to COT, HFNC treatment decreased systolic blood pressure (SBP) at day 1, diastolic blood pressure (DBP) at day 1-4, and heart rate (HR) at day 2-4, increased arterial partial pressure of oxygen (PaO2) at day 1-4, and arterial oxygen saturation (SaO2%) at day 1-2. In addition, the rate of PPCs and anastomotic leakage in HFNC group were lower than those in COT group. Compared to COT, HFNC treatment significantly decreased the amount of lung volume loss caused by PPCs. CONCLUSIONS: HFNC can improve the hypoxemia of patients after esophagectomy, increase the flow of sputum, reduce the incidence of PPC and anastomotic leakage.

p62 Suppressed VK3-induced Oxidative Damage Through Keap1/Nrf2 Pathway In Human Ovarian Cancer Cells.

Imbalance of redox homeostasis may be responsible for the resistance of cancer to chemotherapy. Currently, increasing studies demonstrated that vitamin K3 (VK3), which promoted the production of ROS, had potential to be developed as an anti-tumor agent. We found SKOV3/DDP cells with high levels of p62 were insensitive to VK3 compared with SKOV3 cells. Furthermore, Nrf2 downstream antioxidant genes such as HO-1(heme oxygenase 1) and NQO1 (NAD (P) H: quinone oxidoreductase 1) were upregulated in SKOV3/DDP cells with VK3 treatment, which indicated VK3 activated Nrf2 signaling in SKOV3/DDP cells. Moreover, co-localization of p62 and Keap1 was also observed. Suppression of p62 expression increased the apoptosis induced by VK3, and the expression of Nrf2, HO-1 and NQO1 were all downregulated in SKOV3/DDP cells. Our results suggested that overexpressed p62 may protect cells from oxidative damage caused by VK3 through activating Keap1/Nrf2 signaling in ovarian cancer.

ABO blood group and risk of newly diagnosed nonalcoholic fatty liver disease: A case-control study in Han Chinese population.

BACKGROUND: ABO blood group has been associated with cardiovascular disease and cancer. However, whether ABO blood group is associated with nonalcoholic fatty liver disease (NAFLD) remains unknown. The present study aimed to clarify this issue. METHODS: A hospital-based case-control study was performed in southwestern China. A total of 583 newly ultrasound-diagnosed NAFLD cases and 2068 controls were included. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of developing NAFLD were calculated by multivariate logistic regression. A propensity score was developed for adjustment and matching. RESULTS: The proportions of blood groups A, B, AB and O were 31%, 26%, 8% and 35%, respectively. Non-O blood groups were found to be significantly associated with an increased risk of NAFLD (the fully adjusted OR = 1.51, 95% CI: 1.19, 1.91); moreover, compared with blood group O, the fully adjusted ORs of developing NAFLD were 1.50 (95% CI: 1.13, 1.99) for blood group A, 1.59 (95% CI: 1.19, 2.14) for blood group B, and 1.37 (95% CI: 0.86, 2.18) for blood group AB. Similar results were obtained in both propensity-score-adjusted and propensity-score-matched analyses. No evidence of significant effect modification for the association of ABO blood group with the risk of NAFLD was found (all Pinteraction>0.05). CONCLUSIONS: Non-O blood groups are significantly associated with an increased risk of NAFLD. Our findings provide some epidemiological evidence for a possible role of ABO glycosyltransferase in the pathogenesis of NAFLD. However, these findings need to be validated by future studies.

Development of Multifunctional Clay-Based Nanomedicine for Elimination of Primary Invasive Breast Cancer and Prevention of Its Lung Metastasis and Distant Inoculation.

Cancer recurrence and metastasis are worldwide challenges but current bimodular strategies such as combined radiotherapy and chemotherapy (CTX), and photothermal therapy (PTT) and immunotherapy have succeeded only in some limited cases. Thus in the present study, a multifunctional nanomedicine has been rationally designed via elegantly integrating three FDA-approved therapeutics, that is, indocyanine green (for PTT), doxorubicin (for CTX), and CpG (for immunotherapy) into the structure of layered double hydroxide (LDH) nanoparticles, aiming to completely prevent the recurrence and metastasis of invasive breast cancer. This multifunctional hybrid nanomedicine has been demonstrated to eliminate the primary tumor and efficiently prevent tumor recurrence and lung metastasis through combined PTT/CTX and induction of specific and strong immune responses mediated by the hybrid nanomedicine in a 4T1 breast cancer mouse model. Furthermore, the promoted in situ immunity has significantly inhibited the growth of reinoculated distant tumors. Altogether, our multifunctional LDH-based nanomedicine has showed an excellent efficacy in invasive cancer treatment using much lower doses of three FDA-approved therapeutics, providing a preclinical/clinical alternative to cost-effectively treat invasive breast cancer.

Extracorporeal membrane oxygenation (ECMO) assisted mediastinal tumor resection and superior vena cava replacement are safe and feasible.

BACKGROUND: How to maximally improve the drainage of intracranial and upper body venous and to reduce neurological complications during thoracic tumor-causedsuperior vena cava replacement are still clinical problems to be solved. METHODS: We have innovatively used the bilateral jugular vein-left femoral vein ECMO shunting to perform mediastinal tumor resection and superior vena cava replacement in a 50-year-old woman. RESULTS: During the operation, this technique maintained the patient's hemodynamic stability, improved the cerebral oxygen saturation and reduced the cerebral ischemia, hypoxia as well as the neurological complications. CONCLUSION: It is indicated for patients with superior vena cava replacement who are unable to perform venous bypass (such as innominate vein to right atrial bypass) or venous shunting (such as differential pressure drainage from internal jugular vein to femoral vein).

Extracorporeal membrane oxygenation (ECMO)-assisted intratracheal tumor resection and carina reconstruction: A safer and more effective technique for resection and reconstruction.

Carina resection and reconstruction is required when a tracheal tumor invades the tracheal carina. It is a relatively complicated surgical procedure that requires complex reconstruction to maintain airway continuity. The technical difficulty lies in minimizing the influence of anesthetic endotracheal intubation and maintaining good ventilation function during surgery by establishing appropriate ventilation channels, which are contradictory in many cases. Therefore, in order to achieve the optimal surgical outcome, we performed intratracheal tumor resection and carina reconstruction with the help of extracorporeal membrane oxygenation.

Molecular Weight-Dependent Immunostimulative Activity of Low Molecular Weight Chitosan via Regulating NF-κB and AP-1 Signaling Pathways in RAW264.7 Macrophages.

Chitosan and its derivatives such as low molecular weight chitosans (LMWCs) have been found to possess many important biological properties, such as antioxidant and antitumor effects. In our previous study, LMWCs were found to elicit a strong immunomodulatory response in macrophages dependent on molecular weight. Herein we further investigated the molecular weight-dependent immunostimulative activity of LMWCs and elucidated its mechanism of action on RAW264.7 macrophages. LMWCs (3 kDa and 50 kDa of molecular weight) could significantly enhance the mRNA expression levels of COX-2, IL-10 and MCP-1 in a molecular weight and concentration-dependent manner. The results suggested that LMWCs elicited a significant immunomodulatory response, which was dependent on the dose and the molecular weight. Regarding the possible molecular mechanism of action, LMWCs promoted the expression of the genes of key molecules in NF-κB and AP-1 pathways, including IKKß, TRAF6 and JNK1, and induced the phosphorylation of protein IKBα in RAW264.7 macrophage. Moreover, LMWCs increased nuclear translocation of p65 and activation of activator protein-1 (AP-1, C-Jun and C-Fos) in a molecular weight-dependent manner. Taken together, our findings suggested that LMWCs exert immunostimulative activity via activation of NF-κB and AP-1 pathways in RAW264.7 macrophages in a molecular weight-dependent manner and that 3 kDa LMWC shows great potential as a novel agent for the treatment of immune suppression diseases and in future vaccines.

Mycobacterium-Specific γ9δ2 T Cells Mediate Both Pathogen-Inhibitory and CD40 Ligand-Dependent Antigen Presentation Effects Important for Tuberculosis Immunity.

Numerous pathogens, including Mycobacterium tuberculosis, can activate human γ9δ2 T cells to proliferate and express effector mechanisms. γ9δ2 T cells can directly inhibit the growth of intracellular mycobacteria and may also act as antigen-presenting cells (APC). Despite evidence for γδ T cells having the capacity to function as APC, the mechanisms involved and importance of these effects on overall tuberculosis (TB) immunity are unknown. We prepared M. tuberculosis-specific γ9δ2 T cell lines to study their direct protective effects and APC functions for M. tuberculosis-specific αß T cells. The direct inhibitory effects on intracellular mycobacteria were measured, and the enhancing effects on proliferative and effector responses of αß T cells assessed. Furthermore, the importance of cell-to-cell contact and soluble products for γ9δ2 T cell effector responses and APC functions were investigated. We demonstrate, in addition to direct inhibitory effects on intracellular mycobacteria, the following: (i) γ9δ2 T cells enhance the expansion of M. tuberculosis-specific αß T cells and increase the ability of αß T cells to inhibit intracellular mycobacteria; (ii) although soluble mediators are critical for the direct inhibitory effects of γ9δ2 T cells, their APC functions do not require soluble mediators; (iii) the APC functions of γ9δ2 T cells involve cell-to-cell contact that is dependent on CD40-CD40 ligand (CD40L) interactions; and (iv) fully activated CD4(+) αß T cells and γ9δ2 T cells provide similar immune enhancing/APC functions for M. tuberculosis-specific T cells. These effector and helper effects of γ9δ2 T cells further indicate that these T cells should be considered important new targets for new TB vaccines.

Four New Amaryllidaceae Alkaloids from Lycoris radiata and Their Cytotoxicity.

Four new Amaryllidaceae alkaloids, named lycoranines C-F (1-4), together with seven known ones (5-11) were isolated from the bulbs of Lycoris radiata. Their structures with absolute configurations were elucidated by nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, circular dichroism spectra, modified Mosher's method, and molecular modeling calculation. Compounds 6, 7, 10, and 11 exhibited a potent inhibitory effect on A549 and LoVo cells with IC50 values ranging from 3.97 ± 0.36 to 17.37 ± 1.57 µM.

Bcl-2 family proteins are involved in the signal crosstalk between endoplasmic reticulum stress and mitochondrial dysfunction in tumor chemotherapy resistance.

Tumor cells overexpress antiapoptotic proteins of the Bcl-2 (B-cell leukemia/lymphoma-2) family, which can lead to both escape from cell death and resistance to chemotherapeutic drugs. Recent studies suggest that the endoplasmic reticulum (ER) can produce proapoptotic signals, amplifying the apoptotic signaling cascade. The crosstalk between mitochondria and ER plays a decisive role in many cellular events but especially in cell death. Bcl-2 family proteins located in the ER and mitochondria can influence not only the function of the two organelles but also the interaction between them. Therefore, the Bcl-2 family of proteins may also be involved in the mechanism of tumor chemotherapy resistance by influencing crosstalk between the ER and mitochondria. In this review we will briefly discuss evidence to support this concept.

XRCC1 Arg399Gln, Arg194Trp, and Arg280His polymorphisms in esophageal cancer risk: a meta-analysis.

BACKGROUND: The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair. AIM: To elucidate the role of XRCC1 Arg399Gln, Arg194Trp and Arg280His genotypes in esophageal cancer risk, all available studies were considered in the present meta-analysis. METHODS: Eligible studies were identified by searching several electronic databases for relevant reports published before June 2012. RESULTS: According to the inclusion criteria and exclusion criteria, a total of 21 eligible studies were included in the pooled analyses. Among the 21 studies, 18 focused on Arg399Gln polymorphism, 11 described the Arg194Trp, and 4 articles investigated on Arg280His. Our analysis suggested that there was no evidence of significant association between XRCC1 Arg399Gln polymorphism and esophageal cancer risk in any genetic model. In the stratified analysis by ethnicity for Arg399Gln polymorphism and esophageal cancer, the results showed that Arg399Gln polymorphism was not associated with esophageal cancer risk. Only 4 studies analyzed the relationship between XRCC1 Arg280His polymorphism and the risk of esophageal cancer. The Arg/His and His/His genotypes were not significantly associated with increased risk of EC. A similar negative association was maintained in dominant and recessive models. However, for XRCC1 Arg194Trp polymorphism, our study showed individuals carrying the variant genotype Trp/Trp had a significant increased risk of esophageal cancer (OR = 1.295, 95 % CI 1.053-1.591, P = 0.014). In addition, increased associations were found in recessive model (OR = 1.332, 95 % CI 1.093-1.624, P = 0.005). CONCLUSIONS: Our meta-analysis suggested that Arg194Trp Trp allele might act as a risk allele in its association with esophageal cancer.

Granzyme A produced by γ(9)δ(2) T cells induces human macrophages to inhibit growth of an intracellular pathogen.

Human γ(9)δ(2) T cells potently inhibit pathogenic microbes, including intracellular mycobacteria, but the key inhibitory mechanism(s) involved have not been identified. We report a novel mechanism involving the inhibition of intracellular mycobacteria by soluble granzyme A. γ(9)δ(2) T cells produced soluble factors that could pass through 0.45 µm membranes and inhibit intracellular mycobacteria in human monocytes cultured below transwell inserts. Neutralization of TNF-α in co-cultures of infected monocytes and γ(9)δ(2) T cells prevented inhibition, suggesting that TNF-α was the critical inhibitory factor produced by γ(9)δ(2) T cells. However, only siRNA- mediated knockdown of TNF-α in infected monocytes, but not in γ(9)δ(2) T cells, prevented mycobacterial growth inhibition. Investigations of other soluble factors produced by γ(9)δ(2) T cells identified a highly significant correlation between the levels of granzyme A produced and intracellular mycobacterial growth inhibition. Furthermore, purified granzyme A alone induced inhibition of intracellular mycobacteria, while knockdown of granzyme A in γ(9)δ(2) T cell clones blocked their inhibitory effects. The inhibitory mechanism was independent of autophagy, apoptosis, nitric oxide production, type I interferons, Fas/FasL and perforin. These results demonstrate a novel microbial defense mechanism involving granzyme A-mediated triggering of TNF-α production by monocytes leading to intracellular mycobacterial growth suppression. This pathway may provide a protective mechanism relevant for the development of new vaccines and/or immunotherapies for macrophage-resident chronic microbial infections.

Bio-filler from waste shellfish shell: preparation, characterization, and its effect on the mechanical properties on polypropylene composites.

Waste shellfish shell stacking with a significant odor and toxicity which are hazardous to human constitutes a serious environmental hazard. For utilization of waste shellfish shell resource, granule of shellfish shell (SS) was prepared from waste shellfish shell by removing cuticle, crushing, grinding and shearing emulsification and was introduced as a filler to reinforce polypropylene (PP). The mechanical behavior of PP/SS composite shows a higher yield strain, yield strength, tensile strength and elongation at break than traditional commercial calcium carbonate (CC) filled PP. Yield strength of PP/SS composite with 2% SS is improved by 11.1% due to the formation of ß-crystalline PP phase. Using waste SS for producing bio-filler for filling PP is an effective and prospective measure to deal with waste SS, which is valuable for industrial production and practical application as fillers for reinforcing polymers.

The IL-8 gene polymorphisms and the risk of the hepatitis B virus/infected patients.

Interleukin-8 (IL-8) belongs to the superfamily of CXC chemokines, contributing to human cancer progression through potential mitogenic, angiogenic, and motogenic functions. We hypothesize that the functional polymorphism of IL-8 may influence the inflammatory process during pathological stage from hepatitis to hepatocellular carcinoma (HCC). Two polymorphisms in the IL-8 gene (-251A/T and +781C/T) were examined in 160 cases of chronic hepatitis B, 80 cases of hepatitis B virus (HBV)-related liver cirrhosis (LC), 150 cases of HBV-related HCC, and 150 healthy controls using polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing. In the LC group, the AA genotypes were associated with a significantly decreased risk of LC compared with the TT genotype (OR=0.14, 95% CI 0.02-0.87, p=0.035). The data also revealed that subjects with the A allele appeared to have lower susceptibility to LC than those with the T allele (OR=0.48, 95% CI 0.25-0.92, p=0.027). The +781C/T polymorphism of IL-8 was not found relevant to the liver diseases. This study indicated that the IL-8 gene -251 AA genotype might be a protect factor for LC.

Sublytic C5b-9 complexes induce proliferative changes of glomerular mesangial cells in rat Thy-1 nephritis through TRAF6-mediated PI3K-dependent Akt1 activation.

The proliferation of glomerular mesangial cells (GMCs) and secretion of extracellular matrix (ECM) in rat Thy-1 nephritis (Thy-1N), resembling human mesangioproliferative glomerulonephritis (MsPGN), have been studied for many years, but the mechanisms, especially the role of signalling pathway activation and its regulation in GMCs triggered by sublytic C5b-9 complexes in Thy-1N rats remain largely unclear. In the study, the proliferation of GMCs and production of ECM as well as the role of PI3K/Akt and its regulation, both in GMCs induced by sublytic C5b-9 (in vitro) and in the renal tissues of rats with Thy-1N (in vivo), were determined and the results revealed that GMCs proliferation and ECM secretion, both in vitro and in vivo, were notably increased, and that PI3K/Akt1 activation and its regulation, such as TNF receptor-associated factor 6 (TRAF6)-mediated Akt1 ubiquitination and PI3K-dependent Akt1 phosphorylation, were involved in the process of Thy-1N induction. On the other hand, silence of the TRAF6, PI3K or Akt1 genes could obviously diminish the proliferative damages and urinary protein secretion of Thy-1N rats. Together, these data implicated that sublytic C5b-9 complexes in Thy-1N rats could promote GMCs proliferation and ECM production through TRAF6-mediated PI3K-dependent Akt1 activation, in which the ubiquitination and phosphorylation of the Akt1 signal molecule played an important role in the initiation and development of the proliferative changes in the rats with Thy-1N.

Activating transcription factor 3 (ATF3) promotes sublytic C5b-9-induced glomerular mesangial cells apoptosis through up-regulation of Gadd45α and KLF6 gene expression.

The sublytic C5b-9 complexes can result in glomerular mesangial cells (GMCs) apoptosis, which involved in the initiation and development of rat Thy-1 nephritis. Activating transcription factor 3 (ATF3) is an immediate early gene for cells to cope with a variety of stress signals, and our previous study revealed that ATF3 could promote GMCs apoptosis attacked by sublytic C5b-9. But the mechanism of ATF3 promoting GMCs apoptosis triggered by sublytic C5b-9 attack has not been elucidated. In this study, the data showed that the expression of ATF3, growth arrest and DNA damage-45 alpha (Gadd45α), Krüppel-like factor 6 (KLF6) and proliferating cell nuclear antigen (PCNA) in the GMCs in response to sublytic C5b-9 stimulation for the indicated time was significantly increased, and ATF3 expression could lead to GMCs apoptosis through up-regulation of Gadd45α and KLF6, but not up-regulation of PCNA. Furthermore, Gadd45α was identified as a downstream target gene regulated by ATF3 directly, and KLF6 might be regulated by ATF3 in an indirect manner.