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Aim: Vascular endothelial growth factor receptor inhibitors (VEGFRIs) have been common used for recurrent ovarian cancer (ROC), but insufficient high-level evidence on verifying its efficacy and safety. Methods: Randomized controlled trials (RCTs) were searched under eight electronic databases. Stata 14.0 and Review Manager 5.3 were used for data analysis. Certainty of the evidence was assessed using the GRADE profiler. This systematic review (SR) was registered under INPLASY (INPLASY202120019). Conclusion: Totally 23 RCTs involving 2810 patients were included in this SR. Current evidence revealed that VEGFRIs had better efficacy, survival and quality of life in the treatment of ROC. Though VEGFRIs increase some drug-related adverse events (AEs), all the AEs could be manageable in the clinical practice.
The expression of VEGF/VEGF receptors (VEGFRs) in ovarian cancer (OC) tissue was found to be higher than in benign or normal ovarian tissue. Therefore angiogenesis inhibitors play an essential role in OC treatment. Many anti-angiogenic agents have been developed in recent years. The role of small-molecule inhibitors of VEGFRs for recurrent OC (ROC) has demonstrated significant antitumor efficacy. These drugs include Nintedanib, Axitinib, Pazopanib, Sorafenib, Vandetanib, Sunitinib, Cediranib, Ramucirumab and Apatinib, and more are in the way. However, insufficient high-level evidence from systematic reviews (SRs) focused on VEGFRIs for ROC. Therefore, we performed an SR to investigate the efficacy and safety of VEGFRIs for patients with ROC. This SR was registered under INPLASY (INPLASY202120019). Totally 23 RCTs involving 2810 patients were included in this SR. The results indicate that VEGFRIs have better efficacy and survival in the treatment of ROC. Though VEGFRIs increase some drug-related adverse events, all the adverse events could be manageable in clinical practice.
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Background: Rheumatoid arthritis (RA) is a common autoimmune disease with the main symptoms being joint swelling and pain. In severe cases, joint deformity or even complete loss of function occurs. Technetium methylene diphosphonate (99Tc-MDP) is widely used for RA treatment in China, but there are no studies on the effects of 99Tc-MDP on intestinal flora. Objective: To explore the effects of 99Tc-MDP treatment on the composition and function of the intestinal flora and to provide new information on the mechanism of 99Tc-MDP in RA treatment. Methods: Stool samples from RA patients before and after 99Tc-MDP treatment were collected to form two groups (Before and After). Total genomic DNA of the samples was extracted for 16S rRNA gene sequencing. The altered composition of the intestinal flora, the key target bacteria regulated by 99Tc-MDP, and the pathways of action of 99 Tc-MDP were analyzed by bioinformatics. Results: A total of 64 fresh stool samples were collected from 32 RA patients. Compared to the Before group, the After group showed increased Bacteroidetes abundance and decreased Firmicutes abundance. At the genus level, Prevotella increased whereas Escherichia decreased. Both α and ß diversity analyses showed that 99Tc-MDP treatment did not affect gut microbial diversity in RA patients. LEfSe analyses and random forest analyses showed Bacteroidetes, Prevotella, Enterococcus, Escherichia and Ruminococcaceae were the main 99Tc-MDP regulating bacteria. Functional enrichment analysis revealed that the functional differences in gut flora of the two groups centered on Metabolism and Genetic Information Processing. Conclusion: This study revealed differences in the composition of the gut microbiota in RA patients before and after 99Tc-MDP treatment. The therapeutic effect of 99Tc MDP is mainly achieved through Bacteroidetes, Prevotella, and Enterococcus. Regulating metabolism and genetic information processing of gut flora may be the mechanism of 99Tc-MDP in treating RA.
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SUMMARY: Lying-ear deformity refers to an auricle that bends backward excessively, is excessively folded against the head, and has a very prominent antihelix. It usually requires experienced surgeons to perform surgical treatment and a prolonged postoperative recovery process. This article proposes a simple and effective hyaluronic acid injection technique that significantly improves the shape of the outer ear and enhances perceived facial aesthetics. Twenty patients underwent treatment with multiple injections. Measure-related parameters were used to evaluate the postoperative effect, and the results were graded using a visual analog scale. Interrater reliability among graders was evaluated using intraclass correlation coefficients. After treatment, no serious complications, such as infection or embolism, occurred. Six months after the procedure, the average auriculocephalic angle increased from 25.11 ± 9.46 to 32.72 ± 8.29 degrees, the average conchoscaphal angle increased from 87.69 ± 9.06 to 95.94 ± 7.11 degrees, and patients' average visual analog scale score increased from 4.40 ± 1.14 to 8.57 ± 0.68. Interrater reliability was fair to good for visual analog scale before injection and 6 months after injection (intraclass correlation coefficients, 0.49 and 0.45, respectively; both P < 0.001). The patients were satisfied with the injection process and results. This injection protocol improved the shape of the outer ear, resulting in excellent postoperative outcomes.
Subject(s)
Ear Auricle , Plastic Surgery Procedures , Humans , Reproducibility of Results , Ear, External/surgery , Ear Auricle/surgery , Skin Transplantation , Treatment OutcomeABSTRACT
Psoriasis seriously harms people's physical and mental health. More and more people pay attention to improving the psoriasis process by immune cells. Our study alters the course of psoriasis by discovering the effect of ErbB4 on the ratio of Th1/Th17 cells. We detected the expression of ErbB4 in CD4-positive T cells in peripheral blood of clinical patients and clinical samples by qPCR and detected the expression of ErbB4 in mouse samples of the model group. ErbB4 siRNA was designed and transfected into cells. The effect of ErbB4 siRNA on Th1/Th17 cell ratio was observed by flow cytometry. ErbB4 siRNA was transfected into mice by lentivirus infection to observe its effect on psoriasis. Finally, the mechanism of ErbB4 affecting psoriasis was observed by Western Blot. According to the results, ErbB4 is highly expressed in clinical samples of psoriasis and CD4-positive T cells of patients with psoriasis. Inhibition of ErbB4 expression can reduce the proportion of Th1/Th17 cells, improve the pathogenesis of psoriasis and have therapeutic effect on psoriasis. Western Blot results showed that ErbB4 affected psoriasis through the IL23/IL17A signal axis. Our study demonstrates that ErbB4 could be a potential immune target for the treatment of psoriasis.
Subject(s)
Psoriasis , Th17 Cells , Animals , Humans , Mice , Cell Differentiation , Psoriasis/genetics , Psoriasis/drug therapy , RNA, Small Interfering/metabolism , Th1 Cells/metabolism , Th17 Cells/metabolismABSTRACT
Wireless power transfer (WPT) technology has been popularized due to its convenience, safety, and unmanned nature. To improve the transmission performance of couplers and reduce the magnetic field, the designers of such couplers often adopt a combination of coils and substrates: however, the non-ferromagnetic substrate often leads to the enhancement of coil equivalent resistance and the decrease of the efficiency of a WPT system. In the present work, the effect of a substrate on coil equivalent resistance is evaluated by finite element simulation. The effects of the distance between a substrate and a coil and the number of turns of coil on the equivalent resistance of coils are studied. Based on the calculation method of alternating current resistance for Litz-wire, the equivalent resistance reduction method involving use of a coil with substrates is proposed to significantly reduce equivalent resistance of the coil with its substrate. A high-power-density coupler is designed based on the above method. The power densities of a transmitting coil and a receiving coil are only 0.542 W/cm 3 and 0.81 W/cm 3 respectively. When the transmission distance is 200 mm, a power transmission of 3.61 kW is realized, and the efficiency of the coupler and system reaches 94.61% and 92.56%, respectively.
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Objective: To investigate the risk of ovarian malignancy in middle-aged and elderly women with rheumatoid arthritis (RA) and its correlation with disease activity. Methods: 219 middle-aged and elderly (age ≥ 40) female RA patients who were treated at the Department of Rheumatology and Immunology of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from August 2019 to September 2020 were selected. Their general information such as age and medical history was collected. RA disease activity-related indicators include rheumatoid factor (RF), anticyclic citrullinated peptide antibody (ACPA), ESR, CRP, and ovarian malignancy risk-related indicators including alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), CA125, CA199, and human epididymis protein 4 (HE4) were detected. According to Risk of Ovarian Malignancy Algorithm (ROMA), they were divided into a low-risk group (ROMA-low, premenopausal: ROMA ≤ 11.4%, postmenopausal: ROMA ≤ 29.9%) and a high-risk group (ROMA-high, premenopausal: ROMA > 11.4%, postmenopausal: ROMA > 29.9%) for ovarian malignancy. Meanwhile, according to the DAS28-ESR, they were divided into the general disease activity group (DAS28-ESR ≤ 5.1) and the high disease activity group (DAS28-ESR > 5.1). SPSS 25.0 software was used to compare the differences among groups and to analyze the correlation between ovarian malignancy risk and RA disease activity. Results: Compared with the ROMA-low group, the levels of RF, ACCP, CDAI, SDAI, DAS28-ESR, and DAS28-CRP in the ROMA-high group were significantly increased (P < 0.05). HE4 and ROMA in the high disease activity group were significantly higher than general disease activity group (P < 0.05). Spearman correlation analysis showed that age (r = 0.472), RF (r = 0.221), ACPA (r = 0.156), CDAI (r = 0.226), SDAI (r = 0.221), DAS28-ESR (r = 0.254), DAS28-CRP (r = 0.208), medications (r = 0.189), and CA199 (r = 0.250) were correlated with ROMA (P < 0.05). Multivariate regression analysis showed that ESR (OR = 1.11), SDAI (OR = 1.02), DAS28-ESR (OR = 1.33), DAS28-CRP (OR = 1.26), and CA199 (OR = 1.03) were independent risk factors for high risk of ovarian malignancy (P < 0.05). Subgroup analysis showed that CA199 is an effect modification factor for DAS28-ESR (P < 0.05). Conclusion: The risk of ovarian malignancy is significantly increased in middle-aged and elderly women with high disease activity with rheumatoid arthritis. In clinical, full attention should be paid to the risk of ovarian malignancy in this population. Screening in time, especially in patients with increased DAS28-ESR and CA199 at the same time, is needed.
Subject(s)
Arthritis, Rheumatoid , Ovarian Neoplasms , Aged , Arthritis, Rheumatoid/drug therapy , CA-125 Antigen , Female , Humans , Middle Aged , Ovarian Neoplasms/epidemiology , Rheumatoid Factor , Severity of Illness IndexABSTRACT
Doxorubicin-induced cardiomyopathy (DCM) is a life-threatening event. The long noncoding RNAs (lncRNAs) have been reported with close associations with DCM, which may provide novel insight into pathophysiological mechanisms of DCM. DCM rat model and cell models were established using doxorubicin. Echocardiography analyses were performed to assess cardiac function. We found that testis developmental-related gene 1 (TDRG1) expression was upregulated in DCM rats and in doxorubicin-treated human umbilical vein endothelial cells (HUVECs). TDRG1 knockdown enhanced cell viability, promoted tube formation, and inhibited apoptosis of doxorubicin-treated HUVECs. Additionally, knockdown of TDRG1 alleviated cardiac injury in DCM rats. Mechanistically, miR-873-5p was identified to bind with TDRG1. In addition, protein kinase cAMP-dependent type II regulatory subunit alpha (PRKAR2) was confirmed to bind with miR-873-5p as a target mRNA. MiR-873-5p negatively regulated PRKAR2 mRNA and protein levels. At last, rescue assays indicated that the overexpression of PRKAR2 restored the effect of TDRG1 knockdown on doxorubicin-treated HUVEC angiogenesis and apoptosis. To conclude, TDRG1 aggravates DCM progression by binding with miR-873-5p to upregulate PRKAR2. This work suggested the potential of TDRG1 as a target for DCM treatment.
Subject(s)
Cardiomyopathies , MicroRNAs , RNA, Long Noncoding , Animals , Apoptosis/genetics , Cardiomyopathies/chemically induced , Cardiomyopathies/genetics , Doxorubicin , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Male , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Messenger , Rats , Testis/metabolismABSTRACT
Introduction: Respiratory tract infections (RTIs) are a major cause of morbidity and mortality in some high-risk groups including children and older adults. There is evidence that Chinese herbal medicine has an effect on RTIs. Reynoutria japonica Houtt (better known under its synonym Fallopia japonica (Houtt.) Ronse Decr.) (F. japonica), a commonly used Chinese herbal medicine, has a high content of resveratrol and glycosides. In traditional Chinese medicine theory, F. japonica has the effect of clearing heat in the body, improving blood and qi circulation, eliminating phlegm, and relieving cough, so it may have an effect on RTIs. Methods: This systematic review was registered under PROSPERO CRD42020188604. Databases were searched for randomized controlled trials of F. japonica as a single herb, or as a component of a complex herbal formula for RTIs. Quality of methodology was assessed by two reviewers independently using the Cochrane Risk of Bias Tool. The primary outcome was symptom improvement rate. The secondary outcome measures were fever clearance time, Murray lung injury score and incidence of adverse effects. The extracted data were pooled and meta-analysed by RevMan 5.3 software. Results: Eight RCTs with 1,123 participants with acute RTIs were included in this systematic review, and all the RCTs used F. japonica as part of a herbal mixture. Only one included trial used F. japonica in a herbal mixture without antibiotics in the treatment group. The findings showed that herbal remedies that included F. japonica could increase the symptom improvement rate (risk ratio 1.14, 95% confidence intervals [1.09, 1.20], I2 = 0%, p < 0.00001, n = 7 trials, 1,013 participants), shorten fever duration, reduce Murray lung injury score and did not increase adverse events (RR 0.33, 95% CI [0.11, 1.00], I2 = 0%, p = 0.05, n = 5 trials, 676 participants). Conclusion: There is limited but some evidence that F. japonica as part of a herbal mixture may be an effective and safe intervention for acute RTIs in clinical practice. In future studies it would be preferable to evaluate the effectiveness and safety of using F. japonica without antibiotics for acute RTIs.
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BACKGROUND: With a pronounced and historically unprecedented tendency of population ageing, research on ageing and related disorders has been increasingly brought into focus. Horticultural therapy (HT), as an important role of social prescribing, has been an integrative for decades. This systematic review and meta-analysis aimed to evaluate HT for general health in older adults. METHODS: Electronic databases including PubMed, Web of Science, ScienceDirect, the Cochrane Library, MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO), China National Knowledge Infrastructure (CNKI), and the Wanfang database, grey literature databases and clinical trials registers were searched from inception to March 2021. Randomized controlled trials (RCTs), quasi-RCTs (QRCTs) and the cohort studies about HT for adults aged over 60 were included in this study. Outcome measures were physical function, quality of life, BMI, mood tested by self-reported questionnaire and the expression of the immune cells. The study was registered under PROSPERO (CRD42019146184). RESULTS: Totally, fifteen studies (thirteen RCTs and two cohort studies) involving 1046 older participants were included. Meta-analysis showed that HT resulted in better quality of life (MD 2.09, 95% CI [1.33, 2.85], P<0. 01) and physical function (SMD 0.82, 95% [0.36, 1.29], P<0.01) compared with no-gardener; the similar findings showed in BMI (SMD -0.30, 95% [-0.57, -0.04], P = 0.02) and mood tested by self-reported questionnaire (SMD 2.80, 95% CI [1.82, 3.79], P<0. 01). And HT might be conducive on blood pressure and immunity, while all the evidence were moderate-quality judged by GRADE. CONCLUSIONS: HT may improve physical function and quality of life in older adults, reduce BMI and enhance positive mood. A suitable duration of HT may be between 60 to 120 minutes per week lasting 1.5 to 12 months. However, it remains unclear as to what constitutes an optimal recommendation.
Subject(s)
Health Promotion , Horticultural Therapy , Aged , Humans , Middle Aged , Quality of LifeABSTRACT
BACKGROUND: Hypoxia is a crucial factor in the development of esophageal cancer. The relationship between hypoxia and immune status in the esophageal cancer microenvironment is becoming increasingly important in clinical practice. This study aims to clarify and investigate the possible connection between immunotherapy and hypoxia in esophageal cancer. METHODS: The Cancer Genome Atlas databases are used to find two types of esophageal cancer cases. Cox regressions analyses are used to screen genes for hypoxia-related traits. After that, the genetic signature is validated by survival analysis and the construction of ROC curves. GSEA is used to compare differences in enrichment in the two groups and is followed by the CIBERSORT tool to investigate a potentially relevant correlation between immune cells and gene signatures. RESULTS: We found that the esophageal adenocarcinoma hypoxia model contains 3 genes (PGK1, PGM1, SLC2A3), and the esophageal squamous cell carcinoma hypoxia model contains 2 genes (EGFR, ATF3). The findings demonstrated that the survival rate of patients in the high-risk group is lower than in the lower-risk group. Furthermore, we find that three kinds of immune cells (memory activated CD4+ T cells, activated mast cells, and M2 macrophages) have a marked infiltration in the tissues of patients in the high-risk group. Moreover, we find that PD-L1 and CD244 are highly expressed in high-risk groups. CONCLUSIONS: Our data demonstrate that oxygen deprivation is correlated with prognosis and the incidence of immune cell infiltration in patients with both types of esophageal cancer, which provides an immunological perspective for the development of personalized therapy.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Esophageal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Humans , Hypoxia/genetics , Prognosis , Tumor Microenvironment/geneticsABSTRACT
[This corrects the article DOI: 10.1093/asjof/ojaa053.][This corrects the article DOI: 10.1093/asjof/ojab011.].
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An increasing number of Asian people are seeking nonsurgical facial aesthetic treatments. Ethnic Asians differ from Western populations in both facial appearance and baseline structural facial anatomy. And there is a lack of clinical instruction to doctors who provide facial aesthetic treatment for Asian patients. The authors proposed the " Future Codes" design in Chinese calligraphy describing the art of facial injection in Asians to help doctors perform well. "" are pictograph of 2 Chinese characters, translated into English as "Future," which represent beautiful meanings and vividly describe the procedure and operating area of the design methods. The concept encompasses a systematic overall design for the art of facial injection in Asians, and these procedures are easy to learn and perform safely. This is the first systematic solution available in the clinic that can be used to design facial aesthetics and rejuvenation in Asians through Eastern philosophy and culture.
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Atherosclerosis (AS) is a chronic inflammatory vascular disease characterized by the accumulation of lipids and inflammatory debris in large arteries, high morbidity, and AS-related disease mortality. AS is a complex process, involving endothelial cell dysfunction and inflammation, smooth muscle cell proliferation, and macrophage activation. However, the currently available therapies for AS are not ideal, thus requiring development of novel treatment strategies. Exosomes are bi-lipid membranous extracellular containing multifarious cargo, such as proteins, lipids, micro ribonucleic acid (miRNAs), messenger RNAs, and long non-coding RNAs. Moreover, exosomes reportedly participate in various AS processes. Specifically, stem cell-derived exosomes can regulate the occurrence and development of AS, exhibiting the ability to overcome the limitations associated with AS treatment and stem cell therapy. In this paper, we review the pathological mechanism of AS and discuss the role of exosomes and stem cell-derived exosomes in AS progression. We conclude by suggesting new therapeutic strategies for treating AS with stem cell-derived exosomes in the hope of improving the clinical treatment of AS.
Subject(s)
Atherosclerosis/metabolism , Atherosclerosis/therapy , Exosomes/metabolism , Stem Cells/metabolism , Animals , Atherosclerosis/pathology , Endothelial Cells/metabolism , Endothelial Cells/pathology , Exosomes/pathology , Humans , Macrophages/metabolism , Macrophages/pathology , Stem Cells/pathologyABSTRACT
BACKGROUND: Lymph node involvement could help to predict the prognosis of pathological T1 (pT1, diameters of ≤3 cm) non-small cell lung cancer (NSCLC). This study assessed the clinicopathological factors and associated lymph node involvement in invasive lung adenocarcinoma (IAC) and squamous cell lung cancer (SCC) and the overall and disease-free survival associated with these factors. METHODS: Three hundred and twenty-five patients with pathological T1 NSCLC (253 IAC and 72 SCC) were retrospectively analyzed from a pool of 1094 primary lung cancer patients. The data were assessed using multiple logistic regression, Kaplan-Meier curves and multivariable analyses. RESULTS: Among patients with a ≤30-mm tumor lesion (N = 325), N1 and N2 lymph node involvement was found in 28 (8.6%) and 34 (10.4%) patients, respectively. Lymph node metastasis occurred in 13.0% (33/253) of pT1 IAC patients and 40.3% (29/72) of SCC patients. Carcinoembryonic antigen (CEA) levels, SCC by histology, and tumor lesions larger than 1.0 cm were associated with lymph node involvement (P < 0.0001, <0.0001, and 0.048, respectively). In IAC patients, negative lymph nodes were associated with better overall survival compared with lymph node-positive ones (P = 0.021). No significant difference was observed in SCC patients regardless of lymph node status (P = 0.40). Multivariable Cox analysis revealed that lymph node involvement was an independent prognostic predictor of overall IAC patient survival (P = 0.041), but not of SCC patient survival (P = 0.470). Chemotherapy was administered to 72.2% (52/72) of SCC patients, a significantly higher rate when compared with that of IAC patients (42.3%, 107/253). CONCLUSIONS: Lymph node metastasis was inversely associated with the overall survival of IAP patients, but not with the survival of SCC patients. Patients with pT1 SCC exhibited a significantly higher rate of lymph node involvement when compared with IAC patients. Thus, a systematic lymph node dissection should be performed in pT1 IAC patients, especially in patients with IAC larger than 1.0 cm, for additional treatment selections to improve survival.
Subject(s)
Adenocarcinoma/secondary , Carcinoma, Non-Small-Cell Lung/secondary , Carcinoma, Squamous Cell/secondary , Lung Neoplasms/pathology , Lymph Nodes/pathology , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Squamous Cell/surgery , Female , Follow-Up Studies , Humans , Lung Neoplasms/surgery , Lymph Node Excision , Lymph Nodes/surgery , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Pneumonectomy , Prognosis , Retrospective Studies , Survival RateABSTRACT
OBJECTIVES: Micro-sized lung adenocarcinoma with a tumour of 1.0 cm or less could help identify the patients who would undergo the surgery treatment with limited resection; however, its clinical characteristics and survival rates remain unclear and are to be tested further. METHODS: Histology, lymphatic metastasis, surgical procedure and survival rates of 366 lung adenocarcinoma patients (from January 2007 to December 2013) with a tumour of 2.0 cm or less were analysed retrospectively. Among these patients, 175 had a primary tumour with a diameter of 1.0 cm or less and 191 had a tumour of 1.1-2.0 cm. The survival of 366 patients was evaluated by the restricted mean survival time (RMST) test, and the risk factors were assessed by multivariable analysis. RESULTS: Larger lesion had a significant relation to old age, male sex, preoperatively carcinoembryonic antigen (CEA) positive, invasive adenocarcinoma (IAC) and advanced-stage disease (P < 0.0001, P = 0.001, P = 0.001, P < 0.0001 and P < 0.0001, respectively). Patients with adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma obtained a better prognosis than those with IAC (5-year overall survival rate: 98.5 vs 84.3%, P = 0.001; disease-related survival rate: 98.5 versus 85.2%, P = 0.001). The 5-year overall survival rates of patients with a tumour less than 1.0 cm in comparison with 1.1-2.0 cm were 100.0 and 88.4% (P < 0.001), whereas the 5-year lung adenocarcinoma-specific survival rates were 100.0 and 89.0% (P < 0.001), respectively. Multivariable analysis for prognosis of lung adenocarcinoma patients with a tumour 2.0 cm or less in diameter revealed that histology, lymphatic metastasis and advanced pathological stage affected the 5-year overall and disease-related survival rates unfavourably (P < 0.0001, 0.002, 0.001; and P < 0.0001, 0.005, 0.001, respectively), whereas tumour size did not have an obvious influence on survival. CONCLUSIONS: Micro-sized lung adenocarcinoma (1.0 cm or less) had specific clinical characteristics and more favourable survival rates. These tumours and a subtype of AIS evaluated by computed tomography images or intraoperative frozen section may be appropriate candidates for a limited resection without mediastinal lymph node dissection.
Subject(s)
Adenocarcinoma , Lung Neoplasms , Adenocarcinoma/diagnosis , Adenocarcinoma/epidemiology , Adenocarcinoma/mortality , Adenocarcinoma/physiopathology , Adenocarcinoma of Lung , Adult , Aged , Female , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Lung Neoplasms/mortality , Lung Neoplasms/physiopathology , Male , Middle Aged , Prognosis , Retrospective Studies , Survival AnalysisABSTRACT
Aims. Identification of factors that can predict the subtypes of lung adenocarcinoma preoperatively is important for selecting the appropriate surgical procedure and for predicting postoperative survival. Methods. We retrospectively evaluated 87 patients with lung adenocarcinomas ≤30 mm. Results. Preoperative radiological findings, serum CEA level, serum microRNA-183 (miR-183) level, and tumour size differed significantly between patients with adenocarcinoma in situ (AIS) or minimally invasive adenocarcinoma (MIA) and those with invasive adenocarcinoma (IAC). Receiver operating characteristic curves and univariate analysis revealed that patients who were older than 57 years or had a pure solid nodule or a tumour with mixed ground-glass opacity (mGGO), a tumour >11 mm, a serum CEA level >2.12 ng/mL, or a serum miR-183 level >1.233 (2-ΔΔCt) were more likely to be diagnosed with IAC than with AIS or MIA. The combination of all five factors had an area under the curve of 0.946, with a sensitivity of 89.13% and a specificity of 95.12%. Moreover, patients with a cut-off value >0.499 for the five-factor combination had poor overall survival. Conclusions. The five-factor combination enables clinicians to distinguish AIS or MIA from IAC, thereby aiding in selecting the appropriate treatment, and to predict the prognosis of lung adenocarcinoma patients.
Subject(s)
Adenocarcinoma/pathology , Biomarkers, Tumor/blood , Carcinoembryonic Antigen/blood , Lung Neoplasms/pathology , MicroRNAs/blood , Tomography, X-Ray Computed/methods , Adenocarcinoma/blood , Adenocarcinoma/genetics , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Lung Neoplasms/blood , Lung Neoplasms/genetics , Lung Neoplasms/surgery , Male , MicroRNAs/genetics , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Preoperative Care , Prognosis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Survival RateABSTRACT
T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) has been shown to play an important role in mediating NK-cell function in human diseases. However, the relationship between Tim-3 expression in natural killer (NK) cells and human lung adenocarcinoma remains unclear. We therefore investigated the expression of Tim-3 in NK cells and explored the effect of Tim-3 blockade on NK cell-mediated activity in human lung adenocarcinoma. Upregulated expression of Tim-3 on CD3-CD56+ cells (P<0.05) and CD3-CD56(dim) cells (P<0.05) of patients with lung adenocarcinoma was detected by flow cytometry. Moreover, Tim-3 expression in CD3-CD56+ NK cells was higher in patients with lung adenocarcinoma with lymph node metastasis (LNM) (P<0.05) or with tumor stage T3-T4 (P<0.05). Tim-3 expression in CD56(dim) NK-cell subset was higher in patients with tumor size ≥3cm (P<0.05), or LNM (P<0.05) or with tumor stage T3-T4 (P<0.05). Further analysis showed that higher expressions of Tim-3 on both CD3-CD56+ NK cells and CD56(dim) NK-cell subset were independently correlated with shorter overall survival of patients with lung adenocarcinoma (log-rank test, P=0.0418, 0.0406, respectively). Importantly, blockade of Tim-3 signaling with anti-Tim-3 antibodies resulted in the increased cytotoxicity and IFN-γ production of peripheral NK cells from patients with lung adenocarcinoma. Our data indicate that Tim-3 expression in NK cells can function as a prognostic biomarker in human lung adenocarcinoma and support that Tim-3 could be a new target for an immunotherapeutic strategy.