As one of the most malignant tumors worldwide, lung cancer, fueled by metastasis, has shown rising mortality rates. However, effective clinical strategies aimed at preventing metastasis are lacking owing to its dynamic multi-step, complicated, and progressive nature. Immunotherapy has shown promise in treating cancer metastasis by reversing the immunosuppressive network of the tumor microenvironment. However, drug resistance inevitably develops due to inadequate delivery of immunostimulants and an uncontrolled immune response. Consequently, adverse effects occur, such as autoimmunity, from the non-specific immune activation and non-specific inflammation in off-target organs. Nanocarriers that improve drug solubility, permeability, stability, bioavailability, as well as sustained, controlled, and targeted delivery can effectively overcome drug resistance and enhance the therapeutic effect while reducing adverse effects. In particular, nanomedicine-based immunotherapy can be utilized to target tumor metastasis, presenting a promising therapeutic strategy for lung cancer. Nanotechnology strategies that boost the immunotherapy effect are classified based on the metastatic cascade related to the tumor immune microenvironment; the breaking away of primary tumors, circulating tumor cell dissemination, and premetastatic niche formation cause distant secondary site colonization. In this review, we focus on the opportunities and challenges of integrating immunotherapy with nanoparticle formulation to establish nanotechnology-based immunotherapy by modulating the tumor microenvironment for preclinical and clinical applications in the management of patients with metastatic lung cancer. We also discuss prospects for the emerging field and the clinical translation potential of these techniques.
Humans ; Lung Neoplasms/therapy* ; Tumor Microenvironment ; Neoplasms/drug therapy* ; Immunotherapy/methods*

Relapsing polychondritis is an immune mediated systemic inflammatory disease, involving the cartilaginous and proteoglycan rich structures. The characteristic manifestations were inflammation and deformity of ear and nasal cartilage. Here, Chinese Rheumatology Association summarized manifestations, diagnosis and disease activity index evaluation of relapsing polychondritis, standardized treatment regimens, to improve disease prognosis.

OBJECTIVES: Myocardial ischemia reperfusion injury (IRI) occurs occasionally in the process of ischemic heart disease. Sevoflurane preconditioning has an effect on attenuating IRI. Preserving the structural and functional integrity of mitochondria is the key to reduce myocardial IRI. Silent information regulator 3 (SIRT3), a class of nicotinamide adenine dinucleotide (NAD⁺) dependent deacetylases, is an important signal-regulating molecule in mitochondria. This study aims to explore the role of mitochondrial NAD⁺-SIRT3 pathway in attenuating myocardial IRI in rats by sevoflurane preconditioning. METHODS: A total of 60 male Sprague Dawley (SD) rats were randomly divided into 5 groups (n=12): A sham group (Sham group), an ischemia reperfusion group (IR group), a sevoflurane preconditioning group (Sev group, inhaled 2.5% sevoflurane for 30 min), a sevoflurane preconditioning+SIRT3 inhibitor 3-TYP group (Sev+3-TYP group, inhaled 2.5% sevoflurane for 30 min and received 5 mg/kg 3-TYP), and a 3-TYP group (5 mg/kg 3-TYP). Except for the Sham group, the IR model in the other 4 groups was established by ligating the left anterior descending coronary artery. The size of myocardial infarction was determined by double staining. Serum cardiac troponin I (cTnI) level was measured. The contents of NAD⁺ and ATP, the activities of mitochondrial complexes I, II, and IV, the content of MDA, the activity of SOD, and the changes of mitochondrial permeability were measured. The protein expression levels of SIRT3, SOD2, catalase (CAT), and voltage dependent anion channel 1 (VDAC1) were detected by Western blotting. The ultrastructure of myocardium was observed under transmission electron microscope. MAP and HR were recorded immediately before ischemia (T0), 30 min after ischemia (T1), 30 min after reperfusion (T2), 60 min after reperfusion (T3), and 120 min after reperfusion (T4). RESULTS: After ischemia reperfusion, the content of NAD⁺ in cardiac tissues and the expression level of SIRT3 protein were decreased (both P<0.01), and an obvious myocardial injury occurred, including the increase of myocardial infarction size and serum cTnI level (both P<0.01). Correspondingly, the mitochondria also showed obvious damage on energy metabolism, antioxidant function, and structural integrity, which was manifested as: the activities of mitochondrial complexes I, II, and IV, ATP content, protein expression levels of SOD2 and CAT were decreased, while MDA content, VDAC1 protein expression level and mitochondrial permeability were increased (all P<0.01). Compared with the IR group, the content of NAD⁺ in cardiac tissues and the expression level of SIRT3 protein were increased in the Sev group (both P<0.01); the size of myocardial infarction and the level of serum cTnI were decreased in the Sev group (both P<0.01); the activities of mitochondrial complexes I, II, and IV, ATP content, protein expression levels of SOD2 and CAT were increased, while MDA content, VDAC1 protein expression level, and mitochondrial permeability were decreased in the Sev group (all P<0.01). Compared with the Sev group, the content of NAD⁺ in cardiac tissues and the expression level of SIRT3 protein were decreased in the Sev+3-TYP group (both P<0.01); the size of myocardial infarction and the level of serum cTnI were increased in the Sev+3-TYP group (both P<0.01); the activities of mitochondrial complexes I, II, and IV, ATP content, protein expression levels of SOD2 and CAT were decreased, while MDA content, VDAC1 protein expression level, and mitochondrial permeability were increased in the Sev+3-TYP group (all P<0.01). CONCLUSIONS Sevoflurane preconditioning attenuates myocardial IRI through activating the mitochondrial NAD⁺-SIRT3 pathway to preserve the mitochondrial function.
Adenosine Triphosphate/metabolism* ; Animals ; Male ; Mitochondria/metabolism* ; Myocardial Infarction/metabolism* ; Myocardial Reperfusion Injury/metabolism* ; NAD/metabolism* ; Rats ; Rats, Sprague-Dawley ; Sevoflurane/metabolism* ; Sirtuin 3/metabolism* ; Voltage-Dependent Anion Channel 1/metabolism*

Objective To observe the expression of neural axon guidance molecules Slit3 and Robo receptors in mouse aortic smooth muscle cell(MASMC) and investigate the effect of exogenous Slit3 protein on migration and proliferation of MASMC.Methods The primary cultured MASMC were identified by immunofluorescent assay.The expression of Slit3/Robo signal pathway was detected by RT-PCR and immunocytochemical staining.MASMC were divided into 6 groups:the negative control group (DMEM medium containing bovine serum albumin 86 μg/L),Slit3 0μg/L group (DMEM medium without Slit3),Slit3 24 μg/L group (DMEM medium containing Slit3 24 μg/L),Slit3 40 μg/L group (DMEM medium containing Slit3 40 μg/L),Slit3 80 μg/L group (DMEM medium containing Slit3 80 μg/L) and the positive control group (DMEM medium containing platelet derived growth factor 10 μg/L).The effects of exogenous Slit3 on MASMC proliferation and migration were detected by CCK-8 and scratched cells and transwell chambers respectively.Results (1) The mRNA and protein expressions of Slit2,Slit3,Robo1 and Robo4 were detected in MASMC.mRNA level of Slit2 was lower than Slit3 (P ＜ 0.05) and there were no significant difference between mRNA level of Robo1 and Robo4.(2) The mitogenic responses of MASMC were significantly enhanced in Slit3 24 μg/L group,Slit3 40 μg/L group and Slit3 80 μg/L group compared with negative control group (1.13 ± 0.04,1.19 ± 0.02,1.18 ± 0.08 and 0.64 ± 0.10 respectively,all P ＜0.05).The mitogenic activity of MASMC was the strongest in Slit3 40 μg/L group (compared with positive control group 1.27 ± 0.05,P ＞ 0.05).(3) The autonomous migration activity of MASMC were significantly increased in Slit3 24 μg/L group,Slit3 40 μg/L group,Slit3 80 μg/L group compared with negative control group (cell scratch width were (0.40 ± 0.03) cm,(0.32 ± 0.03) cm,(0.30 ± 0.02) cm and (0.49 ±0.01) cm respectively,all P ＜ 0.05).The autonomous migration activity of MASMC was the strongest in Slit3 80 μg/L group (compared with positive control group (0.22 ± 0.01)cm,P＞ 0.05).The transmembrane migration activity of MASMC were significantly increased in Slit3 24 μg/L group,Slit3 40 μg/L group,Slit3 80 μg/L group compared with negative control group (the number of cell migration were 46.67 ± 2.23,65.33 ± 3.43,81.67 ± 4.22 and 39.33 ± 2.03 respectively,all P ＜ 0.05).The transmembrane migration activity of MASMC was the strongest in Slit3 80 μg/L group (compared with positive control group 84.00 ± 2.02,P ＞ 0.05).Conclusion Slit2,Slit3,Robo1 and Robo4 were expressed in MASMC,and exogenous Slit3 could promote proliferation and migration of MASMC in vitro.

Objective To establish an RP-HPLC method for content determination of oleanolic acid in Stauntonia obovatifoliola Hayata subsp.urophylla.Methods The RP-HPLC with LiChrospher C18 column (250 mm × 4.6 mm, 5μm) was used, acetonitrile-methonal-water-acetic acid-triethylamine (65:12:23:0.04:0.02) was used as mobile phase, with flow rate of 1.0 mL/min, detection wavelength at 210 nm and column temperature at 30℃.Results Oleanolic acid showed good linearity (r=0.999 9) in the range of 0.012 36-0.247 2μg;regressive equation wasY=5.13 × 105X - 6.11 × 102;the average recovery was 97.47%;RSD was 2.35% (n=6).Conclusion The method is simple, accurate and reliable, which can be used to determine the content of oleanolic acid in Stauntonia obovatifoliola Hayata subsp.urophylla.

Objective To observe the effects of Slit2 protein on the proliferation and migration of VSMCs .Methods The VSMCs was cultured in our laboratory .The experiment was divided into two parts ,part one:VSMCs were divided into normal con‐trol group and experimental groups(culture with 50 ,75 ,100 ,125 and 150 ng/mL Slit2 respectively);part two :VSMCs were divided into normal control group ,positive control group(culture with TNF‐α10 ng/mL) and experimental groups(culture with TNF‐α10 ng/mL+Slit2 50 ng/mL ,TNF‐α10 ng/mL+Slit2 75ng/mL ,TNF‐α10 ng/mL+ Slit2 100 ng/mL ,TNF‐α10 ng/mL+ Slit2 125 ng/mL and TNF‐α10 ng/mL+Slit2 150 ng/mL respectively) .To detect proliferation and migration of VSMCs by CCK‐8 and tran‐swell experiment .Results The difference of OD value and numbers of VSMCs has no statistical significance in the presence of Slit 2 (P=0 .516 ,P=0 .52) .The numbers of VSMCs has statistical significance between control and positive control groups (P=0 .00) . The numbers of VSMCs in experimental groups were fewer than positive control group (P<0 .05) ,whereas the difference of OD value still has no statistical significance between experimental and positive groups (P= 0 .173) .Conclusion Recombinant Slit2 could inhibits migration in VSMCs induced by TNF‐α,whereas it has no effect on proliferation of VSMCs .

Objective To study influencing factors in patients with rheumatic diseases.Methods One hundred and twenty patients with rheumatic diseases were selected from November 2013 to February 2014 in our hospital for the study.The influencing factors in patients with rheumatic diseases were obtained by proposed questionnaires,and then the univariate and multivariate Logistic regression analysis were performed to study factors affecting the treatment.Results Patients older than 50 of the observation group accounted for 38％ (18/48),the proportion of farmer,patients with primary school education level or below,and monthly income ＜3 000 RMB was 35％(17/48),60％(29/48),and 46％ (22/48) respectively.Compared with the control group,they were significantly higher than the control group,which were 64％(46/72),58％ (42/72),79％(57/72),65％(47/72) (x2=8.058,P=0.005; x2=6.025,P=0.014; x2=4.986,P=0.226; x2=4.456,P=0.035) respectively.Using the treatment as the dependent variable,age ≥50 years of age,farmer,primary school and lower education level,and monthly income ＜3 000 RMB as the independent variable,we carried out the regression analysis.Age (OR=1.124,95％CI:1.084-7.236),occupation (OR=1.871,95％CI:1.054-7.243),education level (OR=1.982,95％CI:1.157-6.256),monthly income (OR=1.363,95％CI:1.012-8.227) are the influencing factors of rheumatism's treatment.Conclusion The treatment of rheumatic diseases are influenced by many factors,and more societal support should be provided to help patients with rheumatic disease receive professional treatment and better control of the disease.

Objective To investigate the application of field work logs in collection of the disaster information in medical rescue of earthquake.Methods The self-designed work logs were made according to the condition of the wounded in the medical rescue of Lushan earthquake.Through the field work logs,we got first hand information which facilitate statistics,inquiry and subsequent follow-up work.Results By using the field work logs,the rescue workers guaranteed the collection of original data timely and accurately,supplied a number of rich and a-list clinical data and also facilitated the masses in disaster areas looking for their relatives.Conclusions The application of field work logs played a pivotal role in medical rescue of Lushan earthquake.It can be widely extended as a general manner in emergency disaster rescue after further perfection.

OBJECTIVE: To investigate the liver protection mechanisms of MAPK signaling pathway of limb ischemia preconditioning in the late phase. METHODS: Thirty-six adult male New Zealand white rabbits, weighing 1.8-2.0 kg, were randomly divided equally into 3 groups: group C (sham operation), group L (liver ischemia-reperfusion 24 h after limb ischemia preconditioning), group IR (liver ischemia-reperfusion without limb ischemia preconditioning). Serum alanine transaminase (ALT) was measured during ischemia reperfusion. The tissue and cell injury of liver were examined by optical and electron microscopy. Activation of P38MAPK, P44/P42MAPK, and JNK in hepatic tissue was assessed by western blot after 30 min of reperfusion. RESULTS: Serum ALT and cell injury in the liver as examined by optical and electron microscopy was decreased in group L as compared with the group IR. Phosphorylation of P38MAPK, P44/ P42MAPK, and JNK were all increased significantly after 30 min of reperfusion. Phosphorylation of P38MAPK and JNK was reduced by limb ischemia pre-treatment. CONCLUSION Limb ischemia pre-treatment can induce the late phase of preconditioning in rabbit liver through the inhibition of the phosphorylation of P38MAPK and JNK.
Animals ; Extremities ; blood supply ; Ischemic Preconditioning ; methods ; Liver ; blood supply ; MAP Kinase Signaling System ; Male ; Phosphorylation ; Rabbits ; Reperfusion Injury ; prevention & control ; p38 Mitogen-Activated Protein Kinases ; chemistry ; physiology

Objective To observe the expression distribution of bone morphogenetic proteins (BMP) in the spinal cord of normal adult rats. Methods Expression of BMP2, BMP4, and BMP7, and their receptors BMPR Ⅰa, BMPR Ⅰb, and BMP Ⅱ were detected by immunochemistry analysis in the spinal cord of normal adult rats. Results Expression of BMPR Ia or BMPR Ib was observed in the motor neurons of the anterior horn, sensory neurons of the dorsal horn, oligodentrocytes, some microglia, and some astrocytes. Expression of receptor BMPR Ⅱ was found in the oligodentrocytes and motor neurons in the gray matter of anterior horn. It was also expressed in some glial fibrillary acidic protein (GFAP)-positive astrocytes in the white matter but not in the gray matter. BMP2 and BMP4 were not expressed in the spinal cord of normal adult rats by immunohistochemistry. BMP7 was expressed in all the APC-positive oligodentrocytes, all the NeuN-positive motor neurons in the anterior horn, and some astrocytes in the normal spinal cord. Phosphated pSmad 1/5/8 protein was expressed in all the oligodentrocytes, all the neurons, and some astrocytes, especially in the GFAP-positive astrocytes which were RC2-positive radial glia in the subventricular zone.Conclusion BMP7, BMP receptors, and phosphated pSmad 1/5/8 are expressed in many types of cells whereas BMP2 and BMP4 are not expressed in the spinal cord of normal adult rats, which suggests an important function of BMP signal pathway in the neuron and glia of spinal cord.