Lung cancer ranks among the most prevalent and lethal malignancies globally. Its prognostic outcomes are not only contingent upon tumor characteristics and therapeutic interventions but also intricately linked to the nutritional and immune profiles of patients. This article conducts a thorough review of both domestic and international research, providing a comprehensive synthesis of the prognostic value of widely investigated nutritional and immune indicators in the context of lung cancer. The primary objective is to identify optimal prognostic markers in clinical practice, offering guidance for precise post-treatment assessment and early intervention for lung cancer patients.
Objective To investigate the effects of TiotropiumBromide on airway inflammation in a rat model of chronic obstructive pulmonary disease( COPD) . Methods Thirty Wistar rats were randomly divided into three groups. Group A received normal breeding as normal control. Group B and group C received LPS( 200 μg, intratracheally injected at the 1st and the 14th day) and tobacco exposure( from the 2nd day to the 30th day except the 14th day) to establish COPD model. And group C received a nebulized dose of Tiotropium Bromide( 0. 12 mmol / L, 10 minutes) 30 minutes before the tobacco exposure each time. Airway resistance and compliance were measured before sacrificed. Histological examination was performed with Hematoxylin-Eosin staining. The concentrations of IL-8 and LTB4 , total and differential cells counts in bronchoalveolar lavage fluid( BALF) were examined, and the concentrations of IL-8 and LTB4 in blood serum were also examined by ELISA. Results Severe lung inflammation and decreased lung function were demonstrated in the rats in the group B compared with those in the group A. The inflammatory cell counts in BALF, and the levels of IL-8 and LTB4 in BALF and serum were significantly increased in the group B compared with those in the group A. Tiotropium Bromide administration improved the parameters above. Conclusions The results suggest that Tiotropium Bromide can alleviate the lung inflammation and improve the lung function in a rat COPD model. These effects may be exerted through reducing the mediators of inflammation.
Objective Bone marrow mesenchymal stem cells （MSCs） have been suggested to play an important role in the treatment of a variety of pulmonary diseases. The present study was aimed at evaluating the therapeutical effect of MSCs transplantation on emphysematous rats，and explore its influence in local and systemic inflammation. Methods Emphysema rat model was established by cigarette smoking. MSCs were transfected with lentivirus vector carrying green fluorecent protein （GFP） and the transfected MSCs in lung of smoke rats were detected by imaging system for small animals. Thirty-six SD rats were randomly divided into a control group，an emphysema group，and a MSCs transplantation group. The total and differential cell counts in bronchoalveolar lavage fluid （BALF） were measured. TNF-α and IL-1β levels in BALF and serum were measured by ELISA. Malonaldehyde （MDA） level in lung tissue was detected by chromatometry. Emphysema changes were evaluated by mean linear intercept （MLI） of lung under light microscope by HE staining. Results The transfected MSC in different lung lobes were found to be alive at four weeks after intrapulmonary delivery. Compared with the emphysema group，the total cell count in BALF，TNF-α and IL-1β levels in BALF and serum，MDA level in lung tissue and MLI were significantly reduced intheMSCs transplantation group（Plt;0.01）. Conclusions Transplantation of MSCs can mediate down-regulation of TNF-α and IL-1β in BALF and serum，attenuate inflammation，oxidative stress and emphysema change of lung，suggesting that MSCs have significant therapeutic effects on emphysema.
Objective To observe the immune responses of T helper cells 17 ( Th17) to respiratory syncytial virus ( RSV) infection induced lung inflammation in mice, and explore its roles on the host immune responses to RSV.Methods Female BALB/ c mice aged 3 to 5 weeks were randomly divided into a RSV group ( n=18) and a control group ( n = 12) . The mice were intranasally administrated by a 107.5 50% tissue culture infective dose ( TCID50) of RSV in 0.1 mL of culture medium. Sterile medium ( 0.1 mL/ mouse) was used as control. After infected on 1st , 4th, 8th day, the mice were sacrificed, and specimens from the lungs and lymph nodes were collected. The lung sections were stained by hematoxylin-eosin to observe the changes of lung inflammation after RSV infection. IL-17A, IL-17F and IL-23p19 mRNA expressions in the lung tissue were determined by real-time PCR. The frequencies of Th17 subsets in hilar lymph node were analyzed by flow cytometry. Results On 4th day after RSV infection, a typical lung interstitial inflammation was observed. However, this inflammation was alleviated on 8th day after RSV infection. The viral load in the lung tissue on 4th day after RSV infection were 9.208 ±0.548, which was the highest among all RSV subgroups ( P lt;0.001) . IL-23p19 and IL-17A cytokine expressions in the lung tissue were significantly increased on 4th day and 8th day after RSV infection compared with control groups ( P lt;0.01) , and the peak was on 4th day. However, IL-17F mRNA expression in the lung tissue on different day after RSV infection had no significant difference compared with the control group ( P gt;0.05) . The frequencies of Th17 subsets in hilar lymph node on 4th day and 8th day after RSV infection were ( 0.37 ±0.043) % and ( 0.853 ±0.048) % respectively, which were higher than those in control groups ( P lt;0.05) . The frequencies of Th17 on 8th day after RSV infection were significantly higher than that on 4th day after RSV infection ( P lt; 0.01) . Conclusions The expression of IL-17A in the lung tissue is increased and the level of Th17 cells in hilar lymph nodes is also elevated in the lung infected by RSV, which indicates that Th17 cells might be involved in host antiviral immune.
Cerebral amyloid angiopathy (CAA) is an age-dependent disease affecting older subjects. CAA is characterized by lobar intracerebral hemorrhage (ICH), lobar cerebral microbleeds (CMBs), nontraumatic subarachnoid hemorrhage, and cortical superficial siderosis (cSS), which is the main causes of spontaneous intracranial hemorrhage in the elderly. If a patient had experienced dementia, psychiatric symptoms, recurrent or multiple lobar hemorrhage, the possibility of CAA should be considered. Epilepsy can be associated with CAA. Literature studies had found that CAA-related inflammation are predisposing factors for the development of epilepsy. It is a unique subtype of CAA, which is a form of inflammation and a rare clinical manifestation of sporadic CAA. CAA-ri is a special type of central nervous system vasculitis. Once CAA patients had exhibited atypical clinical manifestations, such as headache, epilepsy, behavioral changes, focal neurological signs, consciousness impairment combined with asymmetric T2 weighted magnetic resonance imaging high signal lesions, clinicians had to consider it maybe CAA-ri. Although CAA- ri is rare, timely diagnosis is important because once seizure had occured, which may indicated the inflammation in CAA patients may had reached a very serious level. Therefore, timely identification and treatment are particularly important. Literature shows that most patients responded well to immunosuppressants. Because of its uncommon, researches on epilepsy in CAA mainly focused on case reports currently, and there were many controversies about its pathological mechanism, treatment and prognosis. This article mainly reviews the incidence rate , pathological mechanism, treatment and prognosis of epilepsy in CAA.
ObjectiveTo study the potential protective effects of bone marrow mesenchymal stem cells (BMSCs) on chondrocytes injured by interleukin 1β (IL-1β), and the resistant capacity of chondrocytes when co-cultured indirectly with BMSCs against IL-1β. MethodsSix Sprague Dawley (SD) rats were randomly divided into experimental group (articular cartilage defects) and control group. The content and gene expression of IL-1β were detected at 6 hours after surgical intervention by quantitative real time RCR (qRT-PCR) and ELISA. BMSCs repairing function test: the 18-holes cultured chondrocytes were randomly divided into 3 groups (n=6): cells of blank group were not treated;cells of injured group and co-cultured group were intervened by IL-1β, and Transwell chamber was used to establish co-culture system of BMSCs with chondrocyte in co-cultured group. The mRNA relative expressions of cysteinyl aspartate specific proteinase 3 (Caspase 3), a disintegrin and metalloprotease with Thrombospondin motifs 4 (ADAMTS-4), and ADAMTS-5 were measured via qRT-PCR in chondrocytes, meanwhile Caspase-3 content was detected via ELISA, and the cell apoptosis rate was detected via flow cytometry. BMSCs protecting function test: the 12-holes cultured chondrocytes were randomly divided into 2 groups (n=6), Transwell chamber was used to establish co-culture system of BMSCs with chondrocyte in co-cultured group before the 2 groups were both intervened by IL-1β, then the same detected indexes were taken as the BMSCs repairing function test. ResultsAnimal in vivo studies showed that relative expression of IL-1β mRNA and IL-1β contents were significantly higher in experimental group than control group (P<0.05). BMSCs repair tests showed that mRNA relative expressions of Caspase-3, ADAMTS-4, and ADAMTS-5, Caspase-3 content, and cell apoptosis rate were significantly higher in injured group and co-cultured group than blank group, and in injured group than co-cultured group (P<0.05). BMSCs protect tests showed that mRNA relative expressions of Caspase-3, ADAMTS-4, and ADAMTS-5, Caspase-3 content, and cell apoptosis rate in co-cultured group were significantly lower than those in control group (P<0.05). ConclusionBMSCs, as seed cells for tissue engineering, have potential for applications to anti-inflammation and anti-apoptosis.
ObjectiveTo investigate the expression regulation of inflammation cytokines interleukin 4 (IL-4), IL-6, IL-13, and tumor necrosis factor α (TNF-α) in rats with sciatic nerve defect following olfactory ensheathing cell (OEC) transplantation. MethodsThe primary OEC for cell culture and identification was dissociated from the olfactory bulb of the green fluorescent protein-Sprague Dawley (GFP-SD) rat. One hundred SD rats were randomly divided into 2 groups, and the right sciatic nerve defect (10 mm in length) model was made, then repaired with poly (lactic acid-co-glycolic acid) (PLGA). The mixture of equivalent cultured GFP-OEC and extracellular matrix (ECM) was injected into both ends of PLGA nerve conduit in the experimental group (n=55), and the mixture of DMEM and ECM in the control group (n=45). The general situation of rats was observed after operation. At 6 hours, 1 day, 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, and 6 weeks, the inflammatory cytokines were detected by Western blot. At 2, 4, and 6 weeks, the survival of GFP-OEC was observed in the experimental group. At 9 weeks, HE staining was used to observe the morphology of nerve tissue, and the sensory and motor function and the electrophysiological index were detected. ResultsThe cultured primary cells were GFP-OECs by immunofluorescence staining. Compared with the control group, the experimental group showed significantly increased expression level of IL-4 at 2-6 weeks (P < 0.05), significantly decreased expression level of IL-6 and TNF-α at 3 days and 1 week (P < 0.05) and significantly increased expression level of IL-13 at 1 day and 3-6 weeks (P < 0.05) by Western blot detection. At 2, 4, and 6 weeks, the surviving GFP-OEC of regenerative nerve end was observed in the experimental group under the fluorescence microscope. At 9 weeks, regenerative nerve tissue was loose, and cell morphology was irregular in the experimental group, while the regenerative nerve tissue had vesicular voids and the cell number decreased significantly in the control group. At 9 weeks, the functional recovery of sciatic nerve in the experimental group was better than that of the control group, showing significant difference in the lateral foot retraction time, sciatic nerve function index, muscle action potential latency, and the amplitude of compound muscle action potential (P < 0.05). ConclusionOEC can promote the anti-inflammation cytokines expression of IL-4 and IL-13 and inhibit the pro-inflammatory cytokines expression of IL-6 and TNF-α, which can improve the local inflammatory microenvironment of sciatic nerve and effectively promote the structure and function recovery of sciatic nerve.
ObjectiveTo preliminary explore the effect of decellularized adipose tissue (DAT) combined with vacuum sealing drainage (VSD) on wound inflammation in pigs.MethodsThe DAT was prepared through the process of freeze-thaw, enzymatic digestion, organic solvent extraction, and vacuum freeze-drying. The appearance of DAT was observed before and after freeze-drying. HE staining was used to observe its structure and acellular effect. Eighteen male Bama minipigs were recruited, and four dorsal skin soft tissue wounds in diameter of 4 cm were made on each pig and randomly divided into 4 groups for different treatments. The wounds were treated with DAT combined with VSD in DAT/VSD group, DAT in DAT group, VSD in VSD group, and sterile gauze dressing in control group. HE staining was performed at 3, 7, 10, and 14 days after treatment. Moreover, the expressions of inflammatory factors [interleukin 1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α)], as well as the phenotypes of M1 and M2 macrophage phenotypic markers [inducible nitric oxide synthase (iNOS) and arginase 1 (ARG-1)] were detected by real-time fluorescence quantitative PCR (qRT-PCR). ELISA was used to determine the content of iNOS and ARG-1.ResultsGeneral observation and HE staining showed that DAT obtained in this study had a loose porous structure without cells. The neutrophils of wounds were significantly less in DAT/VSD group than in control group and DAT group (P<0.05) at 3 days after treatment, and the difference was not significant (P>0.05) between DAT/VSD group and VSD group. And the neutrophils were significantly less in DAT/VSD group than in other three groups (P<0.05) at 7, 10, and 14 days. The mRNA expressions of IL-1β, IL-6, TNF-α, and iNOS were significantly lower in DAT/VSD group than in other three groups at 3, 7, 10, and 14 days (P<0.05), while the mRNA expression of ARG-1 was significantly higher in DAT/VSD group than in other three groups (P<0.05). ELISA showed that the content of iNOS was significantly lower in DAT/VSD group than in other three groups at 3, 7, 10, and 14 days (P<0.05), while the content of ARG-1 was significantly higher in DAT/VSD group than in other three groups (P<0.05).ConclusionDAT combined with VSD can significantly reduce inflammatory cell infiltration during wound healing, regulate the expressions of inflammatory factors and macrophage phenotype, and the effect is better than single use of each and conventional dressing change.
Objective To explore the association between the preoperative systemic immune-inflammation index (SII) and prognosis in non-small cell lung cancer (NSCLC) patients. Methods A comprehensive literature survey was performed on PubMed, Web of Science, EMbase, The Cochrane Library, Wanfang, and CNKI databases to search the related studies from inception to December 2021. The hazard ratio (HR) and 95% confidence interval (CI) were combined to evaluate the correlation of the preoperative SII with overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) in NSCLC patients. Results A total of 11 studies involving 9 180 patients were eventually included. The combined analysis showed that high SII levels were significantly associated with worse OS (HR=1.61, 95%CI 1.36-1.90, P<0.001), DFS (HR=1.50, 95%CI 1.34-1.68, P<0.001), and RFS (HR=1.17, 95%CI 1.04-1.33, P<0.001). Subgroup analyses also further verified the above results. Conclusion Preoperative SII is a powerful prognostic biomarker for predicting outcome in patients with operable NSCLC and contribute to prognosis evaluation and treatment strategy formulation. However, more well-designed and prospective studies are warranted to verify our findings.
ObjectiveTo explore the factors of affecting the prognosis of pancreatic ductal adenocarcinoma (PDAC) after radical resection based on the preoperative systemic immune-inflammation index (SII) and the controlling nutritional status (CONUT) score and to establish a prognostic prediction model.MethodsThe clinicopathologic data of patients diagnosed with PDAC from January 2014 to December 2019 in the Second Hospital of Lanzhou University were retrospectively analyzed. The X-tile software was used to determine the optimal cut-off value of SII. The Kaplan-Meier method was used to analyze survival. The Cox proportional hazards regression model was used to conduct multivariate analysis of prognostic factors of PDAC after radical surgery. R4.0.5 software was used to draw a nomogram prediction model of 1-, 2-, and 3-year survival rates, then evaluate the effectiveness of the prediction model and establish a web page calculator.ResultsA total of 131 patients were included in the study. The median survival time was 18.6 months, and the cumulative survival rates at 1-, 2-, and 3-year were 73.86%, 36.44%, and 11.95%, respectively. The optimal cut-off value of preoperative SII was 313.1, and the prognosis of patients with SII>313.1 was worse than SII≤313.1 (χ2=8.917, P=0.003). The results of multivariate analysis suggested that the age>65 years old, clinical stage Ⅲ and Ⅳ, preoperative SII>313.1, and CONUT score >4 were the independent factors influencing the prognosis (overall survival) for PDAC after radical resection (P<0.05). The internal verification consistency index (C-index) of the nomogram prediction model including age, clinical stage, preoperative SII, CONUT score and postoperative chemotherapy was 0.669. The survival predicted by the nomogram correction curve fitted well with the observed survival. The decision curve analysis showed that the nomogram prediction model had a wider clinical net benefit (Threshold probability was 0.05–0.95), and the web calculator worked well.ConclusionsAge, clinical stage, preoperative SII, CONUT score are independent influencing factors for prognosis after radical PDAC surgery. Nomogram prediction model included these independent influencing factors is more accurate and web calculator will be more convenient for doctors and patients.