Virtual bronchoscopic navigation with intraoperative cone-beam CT for the diagnosis of peripheral pulmonary nodules.

OBJECTIVE: Transbronchial biopsy is a safe manner with fewer complications than percutaneous transthoracic needle biopsy; however, the current diagnostic yield is still necessitating further improvement. We aimed to evaluate the diagnostic yield of using virtual bronchoscopic navigation (VBN) and cone-beam CT (CBCT) for transbronchial biopsy and to investigate the factors that affected the diagnostic sensitivity. METHODS: We retrospectively investigated 255 patients who underwent VBN-CBCT-guided transbronchial biopsy at our two centers from May 2021 to April 2022. A total of 228 patients with final diagnoses were studied. Patient characteristics including lesion size, lesion location, presence of bronchus sign, lesion type and imaging tool used were collected and analyzed. Diagnostic yield was reported overall and in groups using different imaging tools. RESULTS: The median size of lesion was 21 mm (range of 15.5-29 mm) with 46.1% less than 2 cm in diameter. Bronchus sign was present in 87.7% of the patients. The overall diagnostic yield was 82.1%, and sensitivity for malignancy was 66.3%. Patients with lesion > 2 cm or with bronchus sign were shown to have a significantly higher diagnostic yield. Four patients had bleeding and no pneumothorax occurred. CONCLUSION: Guided bronchoscopy with VBN and CBCT was an effective diagnostic method and was associated with a high diagnostic yield in a safe manner. In addition, the multivariant analysis suggested that lesion size and presence of bronchus sign could be a predictive factor for successful bronchoscopic diagnosis.

Roles and inhibitors of FAK in cancer: current advances and future directions.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that exhibits high expression in various tumors and is associated with a poor prognosis. FAK activation promotes tumor growth, invasion, metastasis, and angiogenesis via both kinase-dependent and kinase-independent pathways. Moreover, FAK is crucial for sustaining the tumor microenvironment. The inhibition of FAK impedes tumorigenesis, metastasis, and drug resistance in cancer. Therefore, developing targeted inhibitors against FAK presents a promising therapeutic strategy. To date, numerous FAK inhibitors, including IN10018, defactinib, GSK2256098, conteltinib, and APG-2449, have been developed, which have demonstrated positive anti-tumor effects in preclinical studies and are undergoing clinical trials for several types of tumors. Moreover, many novel FAK inhibitors are currently in preclinical studies to advance targeted therapy for tumors with aberrantly activated FAK. The benefits of FAK degraders, especially in terms of their scaffold function, are increasingly evident, holding promising potential for future clinical exploration and breakthroughs. This review aims to clarify FAK's role in cancer, offering a comprehensive overview of the current status and future prospects of FAK-targeted therapy and combination approaches. The goal is to provide valuable insights for advancing anti-cancer treatment strategies.

HER2+ advanced gastric cancer: Current state and opportunities (Review).

Human epidermal growth factor receptor 2 (HER2)+ gastric cancer (GC) is a distinct subtype of GC, accounting for 10­20% of all cases of GC. Although the development of the anti­HER2 monoclonal antibody trastuzumab has markedly improved response rates and prognosis of patients with HER2+ advanced GC (AGC), drug resistance remains a considerable challenge. Therefore, dynamic monitoring of HER2 expression levels can facilitate the identification of patients who may benefit from targeted therapy. Besides trastuzumab, DS­8201 and RC48 have been applied in the treatment of HER2+ AGC, and several novel anti­HER2 therapies are undergoing preclinical/clinical trials. At present, combination immunotherapy with anti­HER2 agents is used as the first­line treatment of this disease subtype. New promising approaches such as chimeric antigen receptor T­cell immunotherapy and cancer vaccines are also being investigated for their potential to improve clinical outcomes. The current review provides new insights that will guide the future application of anti­HER2 therapy by summarizing research progress on targeted therapy drugs for HER2+ AGC and combination treatments.

Correlation analysis between peripheral blood dendritic cell subsets and PD-1 in patients with peritoneal adenocarcinoma.

The aim of this study was to explore the association between differential percentages of dendritic cell (DC) subsets in peripheral blood and malignancy (grade and lymph node metastasis) of peritoneal adenocarcinoma patients and the frequencies of dendritic cell subsets in the normal controls. The peripheral blood of 30 patients with peritoneal adenocarcinoma and 12 healthy controls were collected for multicolor flow cytometry analysis. Peritoneal adenocarcinoma patients were grouped according to the malignant degree (grade and lymph node metastasis). Percentages of myeloid DCs (mDCs) and its subsets MDC1 and MDC2 in DCs were lower in peripheral blood of patients with peritoneal adenocarcinoma than in normal controls. The percentages of plasmacytoid dendritic cells (pDCs) and CD16+mDCs in DCs were higher than in normal controls. Compared with poor differentiation grade, patients with well/moderate differentiation grade had an increased percentage of CD16+mDCs. Contrary to CD16+mDCs, the percentage of MDC1 was lower in the well/moderate differentiation grade group. In patients with no lymph node metastasis, pDCs and CD16+mDCs levels were higher compared with patients with lymph node metastasis. mDCs and MDC1 levels had opposite results. pDCs were positively correlated with CD16+mDCs in peripheral blood of peritoneal patients, as was mDCs and MDC1. CD16+mDCs were negatively correlated with MDC1. The percentages of pDCs and CD16+mDCs in DCs were positively correlated with CD3+CD8+T cells, and pDCs also positively correlated with CD8+PD-1+T cells. Our results revealed that DCs subsets correlated with peritoneal adenocarcinoma malignancy. Dendritic cells play an independent role in the immune function of peritoneal adenocarcinoma.

Correlation analysis between peripheral blood dendritic cell subsets and PD-1 in patients with peritoneal adenocarcinoma

Abstract The aim of this study was to explore the association between differential percentages of dendritic cell (DC) subsets in peripheral blood and malignancy (grade and lymph node metastasis) of peritoneal adenocarcinoma patients and the frequencies of dendritic cell subsets in the normal controls. The peripheral blood of 30 patients with peritoneal adenocarcinoma and 12 healthy controls were collected for multicolor flow cytometry analysis. Peritoneal adenocarcinoma patients were grouped according to the malignant degree (grade and lymph node metastasis). Percentages of myeloid DCs (mDCs) and its subsets MDC1 and MDC2 in DCs were lower in peripheral blood of patients with peritoneal adenocarcinoma than in normal controls. The percentages of plasmacytoid dendritic cells (pDCs) and CD16+mDCs in DCs were higher than in normal controls. Compared with poor differentiation grade, patients with well/moderate differentiation grade had an increased percentage of CD16+mDCs. Contrary to CD16+mDCs, the percentage of MDC1 was lower in the well/moderate differentiation grade group. In patients with no lymph node metastasis, pDCs and CD16+mDCs levels were higher compared with patients with lymph node metastasis. mDCs and MDC1 levels had opposite results. pDCs were positively correlated with CD16+mDCs in peripheral blood of peritoneal patients, as was mDCs and MDC1. CD16+mDCs were negatively correlated with MDC1. The percentages of pDCs and CD16+mDCs in DCs were positively correlated with CD3+CD8+T cells, and pDCs also positively correlated with CD8+PD-1+T cells. Our results revealed that DCs subsets correlated with peritoneal adenocarcinoma malignancy. Dendritic cells play an independent role in the immune function of peritoneal adenocarcinoma.

Low glucose metabolite 3-phosphoglycerate switches PHGDH from serine synthesis to p53 activation to control cell fate.

Glycolytic intermediary metabolites such as fructose-1,6-bisphosphate can serve as signals, controlling metabolic states beyond energy metabolism. However, whether glycolytic metabolites also play a role in controlling cell fate remains unexplored. Here, we find that low levels of glycolytic metabolite 3-phosphoglycerate (3-PGA) can switch phosphoglycerate dehydrogenase (PHGDH) from cataplerosis serine synthesis to pro-apoptotic activation of p53. PHGDH is a p53-binding protein, and when unoccupied by 3-PGA interacts with the scaffold protein AXIN in complex with the kinase HIPK2, both of which are also p53-binding proteins. This leads to the formation of a multivalent p53-binding complex that allows HIPK2 to specifically phosphorylate p53-Ser46 and thereby promote apoptosis. Furthermore, we show that PHGDH mutants (R135W and V261M) that are constitutively bound to 3-PGA abolish p53 activation even under low glucose conditions, while the mutants (T57A and T78A) unable to bind 3-PGA cause constitutive p53 activation and apoptosis in hepatocellular carcinoma (HCC) cells, even in the presence of high glucose. In vivo, PHGDH-T57A induces apoptosis and inhibits the growth of diethylnitrosamine-induced mouse HCC, whereas PHGDH-R135W prevents apoptosis and promotes HCC growth, and knockout of Trp53 abolishes these effects above. Importantly, caloric restriction that lowers whole-body glucose levels can impede HCC growth dependent on PHGDH. Together, these results unveil a mechanism by which glucose availability autonomously controls p53 activity, providing a new paradigm of cell fate control by metabolic substrate availability.

From Basic Science to Clinical Practice: The Role of Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A)/p90 in Cancer.

Cancerous inhibitor of protein phosphatase 2A (CIP2A), initially reported as a tumor-associated antigen (known as p90), is highly expressed in most solid and hematological tumors. The interaction of CIP2A/p90, protein phosphatase 2A (PP2A), and c-Myc can hinder the function of PP2A toward c-Myc S62 induction, thus stabilizing c-Myc protein, which represents a potential role of CIP2A/p90 in tumorigeneses such as cell proliferation, invasion, and migration, as well as cancer drug resistance. The signaling pathways and regulation networks of CIP2A/p90 are complex and not yet fully understood. Many previous studies have also demonstrated that CIP2A/p90 can be used as a potential therapeutic cancer target. In addition, the autoantibody against CIP2A/p90 in sera may be used as a promising biomarker in the diagnosis of certain types of cancer. In this Review, we focus on recent advances relating to CIP2A/p90 and their implications for future research.

Peripheral PD-1 and Tim-3 percentages are associated with primary sites and pathological types of peritoneal neoplasms.

PURPOSE: Programmed death-1 (PD-1) and T cell immunoglobulin and mucin-domain-containing molecule 3(Tim-3) may be used as the biomarkers for the therapy in patients with peritoneal neoplasms. In the current study, the differential percentages of peripheral PD-1 and Tim-3 are explored to investigate whether to associate with primary sites and pathological types of patients with peritoneal neoplasms or not. We also investigated the frequencies of PD-1 and Tim-3 on circulating Lymphocytes, CD3 + T cells, CD3 + CD4 + T cells and CD3 + CD8 + T cells if would correlate with the progression-free survival of peritoneal neoplasms patients. METHODS: 115 patients with peritoneal neoplasms were recruited, subjected to multicolor flow cytometric analyses of the percentages of PD-1 and Tim-3 receptors of circulating Lymphocytes, CD3 + T cells, CD3 + CD4 + T cells and CD3 + CD8 + T cells. The peritoneal neoplasms patients were divided into primary group and secondary group depending on whether the tumor had primary focus and limited to peritoneal tumor or not. Then all the patients were regrouped by the pathological types of neoplasms (adenocarcinoma, mesothelioma, and pseudomyxoma). The secondary peritoneal neoplasms group was divided into the different primary site groups (colon, gastric, gynecology). This study also enrolled 38 cases of normal volunteers. The above markers were explored by flow cytometer, to find the differential levels in peritoneal neoplasms patients compared with normal group in peripheral blood. RESULTS: Higher levels of CD4 + T lymphocytes, CD8 + T lymphocytes, CD45 + PD-1 + lymphocytes, CD3 + PD-1 + T cells, CD3 + CD4 + PD-1 + T cells, CD3 + CD8 + PD-1 + T cells and CD45 + Tim-3 + lymphocytes were found in peritoneal neoplasms group than normal control (the p value was respectively 0.004, 0.047, 0.046, 0.044, 0.014, 0.038 and 0.017). Compared with primary peritoneal neoplasms group, the percentages of CD45 + PD-1 + lymphocytes, CD3 + PD-1 + T cells, and CD3 + CD4 + PD-1 + T cells were increased in the secondary peritoneal neoplasms group (the p value was respectively 0.010, 0.044, and 0.040), while PD-1 did not correlate with the primary sites in secondary group (P > 0.05). Tim-3 had no statistical differences in primary peritoneal neoplasms group compared with secondary group (p > 0.05), but CD45 + Tim-3+% lymphocytes, CD3 + Tim-3+%T cells, and CD3 + CD4 + Tim-3 + T cells were associated with different secondary sites of peritoneal neoplasms (p < 0.05). In the different pathological type groups, the percentages of CD45 + PD-1 + lymphocytes, CD3 + PD-1 + T cells presented the higher levels in adenocarcinoma group compared with mesothelioma group (p = 0.048, p = 0.045). The frequencies of CD45 + PD-1 + lymphocytes and CD3 + PD-1 + T cells in peripheral blood were associated with progression-free survival (PFS). CONCLUSIONS: Our work uncovers peripheral PD-1 and Tim-3 percentages are associated with primary sites and pathological types of peritoneal neoplasms. Those findings might provide important assessment to predict peritoneal neoplasms patients' immunotherapy responses.

PET-based radiomics visualizes tumor-infiltrating CD8 T cell exhaustion to optimize radiotherapy/immunotherapy combination in mouse models of lung cancer.

BACKGROUND: Cumulative preclinical and clinical evidences showed radiotherapy might augment systemic antitumoral responses to immunotherapy for metastatic non-small cell lung cancer, but the optimal timing of combination is still unclear. The overall infiltration and exhausted subpopulations of tumor-infiltrating CD8+ T cells might be a potential biomarker indicating the response to immune checkpoint inhibitors (ICI), the alteration of which is previously uncharacterized during peri-irradiation period, while dynamic monitoring is unavailable via repeated biopsies in clinical practice. METHODS: Basing on tumor-bearing mice model, we investigated the dynamics of overall infiltration and exhausted subpopulations of CD8+ T cells after ablative irradiation. With the understanding of distinct metabolic characteristics accompanied with T cell exhaustion, we developed a PET radiomics approach to identify and visualize T cell exhaustion status. RESULTS: CD8+ T cell infiltration increased from 3 to 14 days after ablative irradiation while terminally exhausted populations significantly predominated CD8+ T cells during late course of this infiltrating period, indicating that 3-7 days post-irradiation might be a potential appropriate window for delivering ICI treatment. A PET radiomics approach was established to differentiate T cell exhaustion status, which fitted well in both ICI and irradiation settings. We also visualized the underlying association of more heterogeneous texture on PET images with progressed T cell exhaustion. CONCLUSIONS: We proposed a non-invasive imaging predictor which accurately assessed heterogeneous T cell exhaustion status relevant to ICI treatment and irradiation, and might serve as a promising solution to timely estimate immune-responsiveness of tumor microenvironment and the optimal timing of combined therapy.

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OBJECTIVES: To investigate the risk factors for acute kidney injury (AKI) after hematopoietic stem cell transplantation (HSCT) in children. METHODS: A retrospective analysis was performed on the medical data of 111 children who underwent HSCT from January 2018 to January 2020. A multivariate logistic regression analysis was used to identify the risk factors for AKI. The Kaplan-Meier survival analysis was used to compare the prognosis in children with different grades of AKI. RESULTS: Graft-versus-host disease (grade Ⅱ-Ⅳ) (OR=4.406, 95%CI: 1.501-12.933, P=0.007), hepatic veno-occlusive disease (OR=4.190, 95%CI: 1.191-14.740, P=0.026), and thrombotic microangiopathy (OR=10.441, 95%CI: 1.148-94.995, P=0.037) were closely associated with the development of AKI after HSCT. The children with stage Ⅲ AKI had a lower 1-year survival rate than those without AKI or with stage Ⅰ AKI or stage Ⅱ AKI (28.6%±12.1% vs 82.8%±5.2%/81.7%±7.4%/68.8%±11.6%; P<0.05). CONCLUSIONS: Children with stage Ⅲ AKI after HSCT have a higher mortality rate. Graft-versus-host disease, hepatic veno-occlusive disease, and thrombotic microangiopathy are closely associated with the development of AKI after HSCT.

Two-dimensional ultrathin Ti3C2 MXene nanosheets coated intraocular lens for synergistic photothermal and NIR-controllable rapamycin releasing therapy against posterior capsule opacification.

Posterior capsule opacification (PCO) is one of the most frequent late-onset complications after cataract surgery. Several kinds of drug-eluting intraocular lenses (IOL) were designed for sustainable drug release to suppress ocular inflammation, the proliferation of lens epithelial cells (LECs) and the development of PCO after cataract surgery. Despite previous advances in this field, the drug-loaded IOLs were limited in ocular toxicity, insufficient drug-loading capacity, and short release time. To prevent PCO and to address these drawbacks, a novel drug-loaded IOL (Rapa@Ti3C2-IOL), prepared from two-dimensional ultrathin Ti3C2 MXene nanosheets and rapamycin (Rapa), was fabricated with a two-step spin coating method in this study. Rapa@Ti3C2 was prepared via electrostatic self-assembly of Ti3C2 and Rapa, with a loading capacity of Rapa at 92%. Ti3C2 was used as a drug delivery reservoir of Rapa. Rapa@Ti3C2-IOL was designed to have the synergistic photothermal and near infrared (NIR)-controllable drug release property. As a result, Rapa@Ti3C2-IOL exhibited the advantages of simple preparation, high light transmittance, excellent photothermal conversion capacity, and NIR-controllable drug release behavior. The Rapa@Ti3C2 coating effectively eliminated the LECs around Rapa@Ti3C2-IOL under a mild 808-nm NIR laser irradiation (1.0 W/cm-2). Moreover, NIR-controllable Rapa release inhibited the migration of LECs and suppressed the inflammatory response after photothermal therapy in vitro. Then, Rapa@Ti3C2-IOL was implanted into chinchilla rabbit eyes, and the effectiveness and biocompatibility to prevent PCO were evaluated for 4 weeks. The Rapa@Ti3C2-IOL implant exhibited excellent PCO prevention ability with the assistance of NIR irradiation and no obvious pathological damage was observed in surrounding healthy tissues. In summary, the present study offers a promising strategy for preventing PCO via ultrathin Ti3C2 MXene nanosheet-based IOLs with synergistic photothermal and NIR-controllable Rapa release properties.

Preclinical studies of the triazolo[1,5-a]pyrimidine derivative WS-716 as a highly potent, specific and orally active P-glycoprotein (P-gp) inhibitor.

Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.

The combination of MnO2@Lipo-coated gefitinib and bevacizumab inhibits the development of non-small cell lung cancer.

It can be found from a large number of cancer treatments that use of anti-cancer drugs alone often presents low efficacy and high side effects. This study aims to develop a new drug carrier with tumor-specific response, controlled release in vivo and high tumor-suppressive property. Inorganic nano-materials MnO2 with pH and glutathione (GSH, abundant in cancer cells) responsiveness were used to construct sustained-release functional nano-liposome to be an excellent in vivo pH-sensitive drug delivery system. Some hydrophilic MnO2, gefitinib (Geb), and bevacizumab (Beb) were encapsulated in the phospholipid vesicles (liposomes), so as to integrate several anti-tumor drugs (MnO2-PDA@Lipo@Geb@Beb) to achieve effective treatment of non-small cell lung cancer (NSCLC). Part of the MnO2 nanorods on the lipid shell had the properties of pH and GSH responsiveness, which could further enhance anti-cancer efficacy. Cell assay results showed that MnO2-PDA@Lipo@Geb@Beb nano-drug had an effective inhibition on A549 cell progression and showed excellent biocompatibility. In vivo results further confirmed that MnO2-PDA@Lipo@Geb@Beb nano-drug could effectively inhibit the growth of NSCLC cells. Overall, it can be inferred from the above experimental results that the nanocomposite drug is expected to be widely used in the clinical application of lung cancer.

Dexrazoxane Alleviated Doxorubicin-Induced Nephropathy in Rats.

INTRODUCTION: Doxorubicin (DOX), an anthracycline antitumor agent, has been widely used against various solid tumors and hematological malignancies. However, the clinical application of DOX is restricted by its multiple organ toxicity including nephrotoxicity. This study investigated the protective effects and mechanisms of dexrazoxane (DZR) against DOX-induced nephropathy in rats. METHODS: Male Sprague Dawley rats received 2.5 mg/kg DOX once a week for 5 consecutive weeks. 24-h urinary protein and renal function injury biomarkers were determined to evaluate the renal function. Histopathological changes and glomerulosclerosis were examined by hematoxylin and eosin and periodic acid-Schiff staining. The change of renal ultrastructure in the DOX-induced rats was observed by the electron microscopy. The renal apoptosis was detected by TUNEL staining and measured the protein expression of Caspase-3, Bcl-2, and Bax. Renal interstitial fibrosis was determined by Masson staining and immunohistochemistry examination. The levels of vimentin, alpha-smooth muscle actin (α-SMA), and transforming growth factor ß (TGF-ß) in kidney tissue were detected by Western blot. RESULTS: DZR pretreatment markedly raised the survival rate and improved the renal dysfunction in DOX-treated rats. DZR ameliorated DOX-induced histopathological lesion of glomerular and tubular and apoptosis. DZR restored the oxidant/antioxidant balance via regulating the levels of MDA, SOD, and TAC. DZR reduced DOX-induced collagen IV deposition and renal interstitial fibrosis and downregulated the fibrosis-related protein expressions of vimentin, α-SMA, and TGF-ß1. CONCLUSION: Our results suggest DZR exerted its protective effects against DOX-induced nephropathy through inhibition of lipid peroxidation, apoptosis, and fibrosis.

Overview on the Role of E-Cadherin in Gastric Cancer: Dysregulation and Clinical Implications.

Gastric cancer is the fifth most common cancer and the third most common cause of cancer death all over the world. E-cadherin encoded by human CDH1 gene plays important roles in tumorigenesis as well as in tumor progression, invasion and metastasis. Full-length E-cadhrin tethered on the cell membrane mainly mediates adherens junctions between cells and is involved in maintaining the normal structure of epithelial tissues. After proteolysis, the extracellular fragment of the full-length E-cadhein is released into the extracellular environment and the blood, which is called soluble E-cadherin (sE-cadherin). sE-cadherin promots invasion and metastasis as a paracrine/autocrine signaling molecule in the progression of various types of cancer including gastric cancer. This review mainly summarizes the dysregulation of E-cadherin and the regulatory roles in the progression, invasion, metastasis, and drug-resistance, as well as its clinical applications in diagnosis, prognosis, and therapeutics of gastric cancer.

Application of Montgomery T-Tube Placement in Treating Cotton-Myer IV Subglottic Airway Atresia after Bi-Level Airway Recanalization.

OBJECTIVE: The purpose of this study is to explore the effectiveness and safety of Montgomery T-tube placement in treating Cotton-Myer IV subglottic airway atresia after bi-level airway recanalization. METHODS: This study is a retrospective study. 11 patients who were treated for IV subglottic airway atresia between January 2017 and January 2019 in the Second Affiliated Hospital of Jiaxing University were involved in this study. The 11 patients all had undergone tracheotomies at our hospital, and they were transferred to the Department of Pulmonary and Critical Care Medicine for Montgomery T-tube placement after bi-level airway recanalization when their subglottic airway was atretic. Patients were observed for their clinical manifestations after placement. The effectiveness of T-tube placement after bi-level airway recanalization was assessed. The incidence of short-term and long-term complications after surgery was assessed. Patients were followed up for 3 to 24 months for evaluating their airway recovery. RESULTS: T-tubes were successfully placed in 11 patients. The atretic airways of all patients were recanalized after treatment. Eight patients got restoration of vocal ability, and 3 patients could only say simple words. None of the patients needed assisted oxygen inhalation. The SpO2 average level was increased from 95 ± 2% before treatment to 97 ± 3% after treatment. Patients had significant relief of cough or sputum, and they had less difficulty in dyspnea. All short- or long-term complications were self-relieved or controlled without further malignant progression after treatment by doctors. The average postoperative extubating time was (14.86 ± 3.62) months. CONCLUSION: The application of Montgomery T-tube placement in treating Cotton-Myer IV subglottic airway atresia after bi-level airway recanalization is well effective and safe for patients, and it can be promoted in clinical treatment.

Immunohistochemical Assessment of Transthyretin Association with Colorectal Adenocarcinoma.

BACKGROUND: To explore the association of transthyretin (TRR) with colorectal cancer (CRC) development and progression. METHODS: This study was conducted on 12 normal colorectal tissue samples, 15 colorectal adenomas, and 39 colorectal adenocarcinoma tissue specimens. TTR expression was assessed by immunohistochemistry, and the results were correlated to clinicopathological characteristics of CRC patients. RESULTS: TTR staining was detected in 16.7% (2/12) of normal colon tissues, 46.7% (7/15) of colorectal adenomas, and 89.7% (35/39) of colorectal adenocarcinoma tissues. TTR staining scores in normal colon tissues, adenoma, and adenocarcinoma were 0.58, 2.27, and 5.40, respectively. G3 grade adenocarcinoma had a higher TTR staining score compared with G2 and G1 grades (8.40, p = 0.0009). Lower TTR expression was significantly associated with metastasis (p = 0.043). CONCLUSIONS: TTR expression is positively correlated with adenoma to CRC progression. Thus, TTR has the potential to serve as a predictive marker in CRC.

Gefitinib encapsulation based on nano-liposomes for enhancing the curative effect of lung cancer.

Gefitinib (GEB) is one of the drugs used for patients with epidermal growth factor receptor (EGFR)-positive mutations in non-small cell lung cancer (NSCLC). However, application of GEB is limited by its low water solubility, stability, and utilization rate, especially the side effects while GEB is given by oral. In this study, nanoliposome was used as a carrier to prepare nanoliposome compound drug (GL) by embedding GEB in the nanoliposome perfectly combined with green nontoxic solvent and thin-film dispersion method. The nanoliposome structure was expected to improve the water solubility and biocompatibility of GEB, thus improving the effect of cancer treatment. The surface electronegative nanoliposomes can effectively avoid protein adsorption and prolong the circulation time in vivo. Meanwhile, the ratio of lecithin to cholesterol (LE/CH) was explored to maximize the encapsulation efficiency of nanoliposome. Subsequent test results showed that GL exhibited better stability, smaller particle size and higher encapsulation efficiency. In addition, in vitro drug release curve also further confirmed that GL had a promising drug sustained-release effect. In particular, a series of in vitro tests such as cell activity, apoptosis, colony formation, scratch, invasion, and cell cycle assays were performed. The results indicated that GL significantly enhanced the pro-apoptotic effect on A549 cells. Most cell cycles of A549 cells were blocked in the G0/G1 phase influenced by GL, thus inhibiting the proliferation of cancer cells. In vivo anti-tumor studies showed that compared with pure GEB, GL had a significant inhibiting effect on NSCLC. In conclusion, the GL which was synthesized by a simple method in this study significantly improved the treatment effect of cancer cells, which proved that the nanoliposome carrier had an excellent application prospect in the treatment of lung cancer.

Proto-oncogene Src links lipogenesis via lipin-1 to breast cancer malignancy.

Increased lipogenesis has been linked to an increased cancer risk and poor prognosis; however, the underlying mechanisms remain obscure. Here we show that phosphatidic acid phosphatase (PAP) lipin-1, which generates diglyceride precursors necessary for the synthesis of glycerolipids, interacts with and is a direct substrate of the Src proto-oncogenic tyrosine kinase. Obesity-associated microenvironmental factors and other Src-activating growth factors, including the epidermal growth factor, activate Src and promote Src-mediated lipin-1 phosphorylation on Tyr398, Tyr413 and Tyr795 residues. The tyrosine phosphorylation of lipin-1 markedly increases its PAP activity, accelerating the synthesis of glycerophospholipids and triglyceride. Alteration of the three tyrosine residues to phenylalanine (3YF-lipin-1) disables lipin-1 from mediating Src-enhanced glycerolipid synthesis, cell proliferation and xenograft growth. Re-expression of 3YF-lipin-1 in PyVT;Lpin1-/- mice fails to promote progression and metastasis of mammary tumours. Human breast tumours exhibit increased p-Tyr-lipin-1 levels compared to the adjacent tissues. Importantly, statistical analyses show that levels of p-Tyr-lipin-1 correlate with tumour sizes, lymph node metastasis, time to recurrence and survival of the patients. These results illustrate a direct lipogenesis-promoting role of the pro-oncogenic Src, providing a mechanistic link between obesity-associated mitogenic signaling and breast cancer malignancy.

Efficacy and Safety Profile of Montgomery T-Tube Implantation in Patients with Tracheal Stenosis.

Background: Tracheal stenosis is able to lead to airway obstruction. Objective: To evaluate the efficacy and safety profile of Montgomery T-tube implantation in patients with tracheal stenosis. Methods: Fifty-two patients with tracheal stenosis diagnosed between 2016 and 2019 were included in this retrospective cohort study. The patients were divided into observation group (n = 25 cases) and control group (n = 27). The therapeutic effect, arterial blood gas analysis, arterial oxygen partial pressure (PaO2), arterial carbon dioxide partial pressure (PaCO2), shortness of breath score, airway diameter change, dyspnea score, quality of life, and safety were compared between the two groups before and after treatment. Results: The therapeutic effect of the observation group gained better results than that of the control group (84.00% vs. 62.96%). One week after operation, the pH value, SaO2, PaCO2, shortness of breath score, airway diameter change, dyspnea score, life quality, and incidence of postoperative complications in the observation group exerted better results as compared to the control group. Conclusion: The implantation of Montgomery T-tube has effective function in terms of improving the symptoms of dyspnea and the life quality of patients with safety profile in patients harboring tracheal stenosis.