KIF2C: An important factor involved in signaling pathways, immune infiltration, and DNA damage repair in tumorigenesis.

BACKGROUNDS: Poorly regulated mitosis and chromosomal instability are common characteristics in malignant tumor cells. Kinesin family member 2 C (KIF2C), also known as mitotic centromere-associated kinesin (MCAK) is an essential component during mitotic regulation. In recent years, KIF2C was shown to be dysregulated in several tumors and was involved in many aspects of tumor self-regulation. Research on KIF2C may be a new direction and target for anti-tumor therapy. OBJECT: The article aims at reviewing current literatures and summarizing the research status of KIF2C in malignant tumors as well as the oncogenic signaling pathways associated with KIF2C and its role in immune infiltration. RESULT: In this review, we summarize the KIF2C mechanisms and signaling pathways in different malignant tumors, and briefly describe its involvement in pathways related to classical chemotherapeutic drug resistance, such as MEK/ERK, mTOR, Wnt/ß-catenin, P53 and TGF-ß1/Smad pathways. KIF2C upregulation was shown to promote tumor cell migration, invasion, chemotherapy resistance and inhibit DNA damage repair. It was also highly correlated with microRNAs, and CD4 +T cell and CD8 +T cell tumor immune infiltration. CONCLUSION: This review shows that KIF2C may function as a new anticancer drug target with great potential for malignant tumor treatment and the mitigation of chemotherapy resistance.

Integrative pan-cancer analysis and clinical characterization of the N7-methylguanosine (m7G) RNA modification regulators in human cancers.

Background: RNA modification is one of the epigenetic mechanisms that regulates post-transcriptional gene expression, and abnormal RNA modifications have been reported to play important roles in tumorigenesis. N7-methylguanosine (m7G) is an essential modification at the 5' cap of human mRNA. However, a systematic and pan-cancer analysis of the clinical relevance of m7G related regulatory genes is still lacking. Methods: We used univariate Cox model and Kaplan-Meier analysis to generate the forest plot of OS, PFI, DSS and identified the correlation between the altered expression of m7G regulators and patient survival in 33 cancer types from the TCGA and GTEx databases. Then, the "estimate" R-package, ssGSEA and CIBERSORT were used to depict the pan-cancer immune landscape. Through Spearman's correlation test, we analyzed the correlation between m7G regulators and the tumor microenvironment (TME), immune subtype, and drug sensitivity of the tumors, which was further validated in NSCLC. We also assessed the changes in the expression of m7G related regulatory genes in NSCLC with regards to the genetic and transcriptional aspects and evaluated the correlation of METTL1 and WDR4 expression with TMB, MSI and immunotherapy in pan-cancer. Results: High expression of most of the m7G regulators was significantly associated with worse prognosis. Correlation analyses revealed that the expression of majority of the m7G regulators was correlated with tumor immune infiltration and tumor stem cell scores. Drug sensitivity analysis showed that the expression of CYFP1,2 was closely related to drug sensitivity for various anticancer agents (p < 0.001). Analysis of the pan-cancer immune subtype revealed significant differences in the expression of m7G regulators between different immune subtypes (p < 0.001). Additionally, the types and proportions of mutations in METTL1 and WDR4 and their relevance to immunotherapy were further described. Conclusion: Our study is the first to evaluate the correlation between the altered expression of m7G regulators and patient survival, the degree of immune infiltration, TME and drug sensitivity in pan-cancer datasets.

Circular RNA hsa_circ_0003823 promotes the Tumor Progression, Metastasis and Apatinib Resistance of Esophageal Squamous Cell Carcinoma by miR-607/CRISP3 Axis.

Background: Circular RNAs (CircRNAs) have attracted a growing interest of research in cancer. The regulatory roles and mechanisms of circRNAs in progression, metastasis and drug resistance of esophageal squamous cell carcinoma (ESCC) needed to be clarified. Our previous study revealed the crucial role of Apatinib in ESCC therapy. However, the correlation between circRNAs and Apatinib resistance remained unclear. Methods: 3 pairs of tumor and paracancerous tissues of ESCC patients were used for RNA sequencing. Western blot analysis, RNA immunoprecipitation (RIP), dual-luciferase reporter assays, apoptosis and animal assays were conducted to confirm the roles and specific mechanisms of hsa_circ_0003823 as well as the effects of it on Apatinib sensitivity in ESCC. Results: Our results revealed that hsa_circ_0003823 was highly expressed in ESCC and associated with poor prognosis. Further results indicated that hsa_circ_0003823 promoted proliferation and metastasis ability of ESCC. In the section of mechanism experiments, hsa_circ_0003823 regulated CRISP3 by targeting microRNA-607 (miR-607) to promote progression of ESCC. Besides, we found that silencing hsa_circ_0003823 improved Apatinib sensitivity. hsa_circ_0003823 resulted in Apatinib resistance by miR-607/CRISP3 axis. Conclusions: In this study, we elucidated the function of hsa_circ_0003823 and its role in promoting tumor progression, metastasis and Apatinib resistance of ESCC through miR-607/CRISP3 axis.

The difference of auxiliary examination parameters between margin recurrence and granuloma on enhanced computed tomography after sublobar resection.

Background: Imaging examinations following sublobar resection of lung cancer often find thickened neoplasms around the resection margin. Identifying whether the neoplasms are postoperative recurrence or margin granulomas is vitally important. However, the identification mainly depends on the empirical judgment of the imaging department or clinicians in each clinical center at present, and there are few relevant studies, so it is hard to formulate a relatively unified standard. Therefore, we collected data from patients with thickened neoplasms around the resection margin after sublobar resection and sought to discover how to differentiate granulomas from tumor recurrence. Methods: We examined the clinical records of 15 patients with neoplasms around the margins which identified as malignant in auxiliary examination reports, and received second surgery after first sublobar resection. We collected their postoperative pathology and auxiliary examination parameters. The univariate predictors helpful in distinguishing between recurrence and granuloma were analyzed as a diagnostic test. Results: Of the 15 patients with neoplasms around the resection margin, six were diagnosed with benign granulomas, and nine were diagnosed with primary lung cancer recurrence. The results revealed that age, gender, specific surgical method, maximum standardized fluorodeoxyglucose uptake value (SUVmax), and follow-up time were not significantly different, but there were significant differences in enhanced computed tomography (CT) values in several analyses, which calculated by the hospital imaging system. The maximum CT values of the tumor recurrence and granuloma were 104.9±8.051 and 130.3±7.017 (P=0.045), the minimum CT values (15.67±5.113 vs. -17.17±4.826, P=0.0007) and in the floating range CT values (148.00±5.471 vs. 88.11±7.671, P<0.0001), respectively. Conclusions: Differentiating between tumor recurrence and granulomas after sublobar resection remains difficult. However, examining the differences in enhanced CT allows the clinician to make an informed diagnosis that aids further investigation and treatment.

Mantle cell lymphoma with endobronchial involvement: A case report.

BACKGROUND: Mantle cell lymphoma (MCL) is a subtype of Non-Hodgkin's lymphoma (NHL). MCL frequently affects extranodal sites while endobronchial involvement is uncommon. Only 5 cases of MCL with endobronchial involvement have been previously reported. CASE SUMMARY: A 56-year-old male patient arrived at the hospital complaining of a dry cough. A mass in the right upper lobe of the lung was revealed in Chest computed tomography (CT). Right lung hilar and mediastinal lymphadenopathies were also found by CT scan. The patient was diagnosed with central-type lung cancer with multiple lymph node metastases after positron emission tomography (PET) CT scan examination. The fiber optic bronchoscope examination revealed diffuse neoplasm infiltration in the inlet of the right up lobar bronchus. The patient was finally diagnosed with MCL based on the bronchoscopy and mediastinoscopy biopsy results. CONCLUSION: MCL could masquerade as central type lung cancer. An endobronchial biopsy examination is necessary for the early diagnosis of MCL.

Oridonin Ameliorates Traumatic Brain Injury-Induced Neurological Damage by Improving Mitochondrial Function and Antioxidant Capacity and Suppressing Neuroinflammation through the Nrf2 Pathway.

Traumatic brain injury (TBI) is a global public health concern, and few effective treatments for its delayed damages are available. Oridonin (Ori) recently has been reported to show a promising neuroprotective efficacy, but its potential therapeutic effect on TBI has not been thoroughly elucidated. The TBI mouse models were established and treated with Ori or vehicle 30 min post-operation and every 24 h since then. Impairments in cognitive and motor function and neuropathological changes were evaluated and compared. The therapeutic efficacy and mechanisms of action of Ori were further investigated using animal tissues and cell cultures. Ori restored motor function and cognition after TBI-induced impairment and exerted neuroprotective effects by reducing cerebral edema and cortical lesion volume. Ori increased neuronal survival, ameliorating gliosis and the accumulation of macrophages after injury. It suppressed the increased production of reactive oxygen species, lipid peroxide, and malondialdehyde and reversed the decrease of mitochondrial membrane potential and adenosine triphosphate content, which was also identified in oxidatively stressed neuronal cultures. Further, Ori inhibited the expression of nucleotide-binding domain leucine-rich repeats family protein 3 (NLRP3) inflammasome proteins and NLRP3-dependent cytokine interleukin-1ß that can be induced by oxidative stress after TBI. Regarding underlying mechanisms, Ori significantly enhanced expression of key proteins of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway. Our results demonstrated that Ori effectively improved functional impairments and neuropathological changes in animals with TBI. By activating the Nrf2 pathway, it improved mitochondrial function and antioxidant capacity and suppressed the neuroinflammation induced by oxidative stress. The results therefore suggest Ori as a potent candidate for managing neurological damage after TBI.

Establishment and validation a prediction model for discrimination of invasive adenocarcinomas for patients with peripheral pulmonary subsolid nodules.

Background: The optimal management of patients with subsolid pulmonary nodules is of growing clinical concern. This study sought to develop and validate a more precise predictive model to evaluate the pathological invasiveness of patients with lung peripheral subsolid nodules (SSNs). Methods: The data of 1,140 patients with peripheral SSNs who underwent surgical resection at Shanghai Renji Hospital from January 2014 to December 2018 were retrospectively analyzed. The patients were randomly assigned to a training and validation cohort (at a ratio of 2 to 1). Clinical parameters and imaging features were collected to estimate the independent predictors of pathological invasiveness of SSNs. A nomogram model was developed and applied to the validation cohort. The predictive performance of the nomogram model was evaluated by a calibration curve analysis, an area under the receiver operating characteristic curve (AUC) analysis, and a decision curve analysis (DCA), which was also compared with other diagnostic models. Results: In the multivariate analysis, the nodule diameter (P<0.001), solid component size (P<0.001), mean CT attenuation (P=0.001), spiculation (P<0.001), and pleura indentation (P=0.011) were identified as independent predictors of the pathological invasiveness of SSNs. A nomogram model based on the results of the multivariate analysis was developed and showed a robust discrimination in the validation cohort, with an AUC of [0.890; 95% confidence interval (CI), 0873-0.907], which was higher than another two reported models. The calibration curve showed optimal agreement between the pathological invasive probability as predicted by the nomogram and the actual probability. Conclusions: We developed and validated a nomogram model to evaluate the risk of the pathological invasiveness for patients with lung SSNs. The AUC of this nomogram model was higher than another two reported models. Our nomogram model may help clinicians to make individualized treatment more precisely.

Apatinib induces endoplasmic reticulum stress-mediated apoptosis and autophagy and potentiates cell sensitivity to paclitaxel via the IRE-1α-AKT-mTOR pathway in esophageal squamous cell carcinoma.

BACKGROUND: Apatinib, a novel vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, has been approved for the treatment of metastatic gastric cancer and other tumors. Apatinib exerts antiproliferative and proapoptotic effects in different kinds of cancer cells. However, the molecular mechanisms by which apatinib effective against esophageal squamous cell carcinoma (ESCC) have only been partially researched and whether it has a sensitizing effect on paclitaxel remains unclear. MATERIALS AND METHODS: The effects of apatinib or paclitaxel on endoplasmic reticulum (ER) stress, autophagy, apoptosis and proliferation of ESCC cell lines were evaluated. Western blot and immunohistochemistry analyses were performed to detect the expression of related genes. The weight and volume of xenograft tumors in mice were measured. RESULTS: In the current study, we elucidated the antiproliferative and ER-stress-mediated autophagy-inducing effects of apatinib on ECA-109 and KYSE-150 esophageal squamous cancer cells and identified the underlying mechanisms of its action. We demonstrated that apatinib not only inhibited the proliferation and induced the apoptosis of ESCC cells, but also activated ER stress and triggered protective autophagy. Moreover, inhibiting autophagy by chloroquine (CQ) enhanced the apatinib-induced apoptosis of ESCC cells through the IRE-1α-AKT-mTOR pathway. In addition, we showed, for the first time, the paclitaxel combined with apatinib and CQ exhibited the best antitumor effect on ESCC both in vivo and in vitro via the IRE-1α-AKT-mTOR pathway. CONCLUSIONS: Our data showed that apatinib induced ER stress, autophagy and apoptosis in ESCC. Inhibiting autophagy by CQ enhanced apatinib-induced apoptosis. The combination of apatinib and CQ sensitized ESCC cells to paclitaxel to induce apoptosis through the IRE-1α-AKT-mTOR signaling pathway, thus providing the basis for its use in innovative anticancer therapeutic strategies.

Determining the invasiveness of pure ground-glass nodules using dual-energy spectral computed tomography.

BACKGROUND: The present work aimed to investigate the clinical application of using quantitative parameters generated in the unenhanced phase (UP) and venous phase (VP) in dual-energy spectral CT for differentiating the invasiveness of pure ground-glass nodule (pGGN). METHODS: Sixty-two patients with 66 pGGNs who underwent preoperative dual-energy spectral CT in UP and VP were evaluated retrospectively. Nodules were divided into three groups based on pathology: adenocarcinoma in situ (AIS, n=19), minimally invasive adenocarcinoma (MIA, n=22) (both in the preinvasive lesion group) and invasive adenocarcinoma (IA, n=25). The iodine concentration (IC) and water content (WC) in nodules were measured in material decomposition images. The nodule CT numbers and slopes(k) were measured on monochromatic images. All measurements, including the maximum diameter of nodules were statistically compared between the AIS-MIA group and IA group. RESULTS: There were significant differences of WC in VP between AIS-MIA group and IA group (P<0.05). The CT attenuation values of the 40-140 keV monochromatic images in UP and VP were significantly higher for the invasive nodules. Logistic regression analysis showed that the maximum nodule diameter [odd ratio (OR) =1.21, 95% CI: 1.050-1.400, P<0.01] and CT number in 130 keV images in venous phase (OR =1.03, 95% CI: 1.014-1.047, P<0.001) independently predicted histological invasiveness. CONCLUSIONS: The quantitative parameters in dual-energy spectral CT in the unenhanced phase and venous phase provide useful information in differentiating preinvasive lesion group from IA group of pGGN, especially the maximum nodule diameter and CT number in the 130 keV images in the venous phase.

Application of intraoperative electrophysiological monitoring in vertebral canal decompression surgery for acute spinal cord injury.

OBJECTIVE: This study aimed to evaluate the joint monitoring of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) in vertebral canal decompression surgery for acute spinal cord injury. METHODS: Twenty-four patients, who were admitted to the hospital for the surgical treatment of spinal cord injury with SEP and MEP monitoring, were assigned to the intraoperative monitoring group (group I). In addition, 24 patients who were admitted to the hospital for the surgical treatment of spinal cord injury without SEP or MEP monitoring were assigned to the control group (group C). RESULTS: In group I, there were significant changes before and after decompression surgery in the P40 latency and amplitude, and in the latency of MEP in the abductor hallucis brevis (AHB), in patients with improved spinal nerve function following surgery. In contrast, there were no significant differences in the P40 latency or amplitude, or the latency of MEP in the AHB, in patients who showed no improvement after surgery. CONCLUSION: In vertebral canal decompression surgery for acute spinal cord injury, the application of joint MEP and SEP monitoring can timely reflect changes in spinal cord function.

Zerumbone ameliorates behavioral impairments and neuropathology in transgenic APP/PS1 mice by suppressing MAPK signaling.

BACKGROUND: Alzheimer's disease (AD) is a major clinical problem, but there is a distinct lack of effective therapeutic drugs for this disease. We investigated the potential therapeutic effects of zerumbone, a subtropical ginger sesquiterpene, in transgenic APP/PS1 mice, rodent models of AD which exhibit cerebral amyloidosis and neuroinflammation. METHODS: The N9 microglial cell line and primary microglial cells were cultured to investigate the effects of zerumbone on microglia. APP/PS1 mice were treated with zerumbone, and non-cognitive and cognitive behavioral impairments were assessed and compared between the treatment and control groups. The animals were then sacrificed, and tissues were collected for further analysis. The potential therapeutic mechanism of zerumbone and the signaling pathways involved were also investigated by RT-PCR, western blot, nitric oxide detection, enzyme-linked immunosorbent assay, immunohistochemistry, immunofluorescence, and flow cytometry analysis. RESULTS: Zerumbone suppressed the expression of pro-inflammatory cytokines and induced a switch in microglial phenotype from the classic inflammatory phenotype to the alternative anti-inflammatory phenotype by inhibiting the mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B signaling pathway in vitro. After a treatment period of 20 days, zerumbone significantly ameliorated deficits in both non-cognitive and cognitive behaviors in transgenic APP/PS1 mice. Zerumbone significantly reduced ß-amyloid deposition and attenuated pro-inflammatory microglial activation in the cortex and hippocampus. Interestingly, zerumbone significantly increased the proportion of anti-inflammatory microglia among all activated microglia, potentially contributing to reduced ß-amyloid deposition by enhancing phagocytosis. Meanwhile, zerumbone also reduced the expression of key molecules of the MAPK pathway, such as p38 and extracellular signal-regulated kinase. CONCLUSIONS: Overall, zerumbone effectively ameliorated behavioral impairments, attenuated neuroinflammation, and reduced ß-amyloid deposition in transgenic APP/PS1 mice. Zerumbone exhibited substantial anti-inflammatory activity in microglial cells and induced a phenotypic switch in microglia from the pro-inflammatory phenotype to the anti-inflammatory phenotype by inhibiting the MAPK signaling pathway, which may play an important role in its neuroprotective effects. Our results suggest that zerumbone is a potential therapeutic agent for human neuroinflammatory and neurodegenerative diseases, in particular AD.

Resolvin D1 ameliorates cognitive impairment following traumatic brain injury via protecting astrocytic mitochondria.

Cognitive impairment is one of the most common and devastating neuropsychiatric sequelae after traumatic brain injury (TBI), and hippocampal neuronal survival plays a causal role in this pathological process. Resolvin D1 (RvD1), an important endogenous specialized pro-resolving mediator, has recently been reported to exert a potent protective effect on mitochondria. This suggests that RvD1 may suppress neuroinflammation and protect astrocytic mitochondria at the same time to play further neuroprotective roles. C57BL/6 mice subjected to TBI using a controlled cortical impact device were used for in vivo experiments. Cultured primary mouse astrocytes and an N2a mouse neuroblastoma cell line were used for in vitro experiments. In TBI mice, RvD1 significantly ameliorated cognitive impairment, suppressed gliosis and alleviated neuronal loss in the hippocampus. To explore the mechanism underlying this activity, we verified that RvD1 can induce a higher level of mitophagy to remove damaged mitochondria and eliminate extra mitochondria-derived reactive oxygen species (mitoROS) by activating ALX4/FPR2 receptors in astrocytes. In an in vitro model, we further confirmed that RvD1 can protect mitochondrial morphology and membrane potential in astrocytes and thereby enhance the survival of neurons. Meanwhile, RvD1 was also shown to increase the expression of brain-derived neurotrophic factor and glutamate aspartate transporter in the hippocampus following TBI, which indicates a possible way by which RvD1 increases the supportive function of astrocytes. These findings suggest that RvD1 may be a potent therapeutic option for ameliorating cognitive impairment following TBI by controlling neuroinflammation and protecting astrocytic mitochondria.

Serological investigation of IgG and IgE antibodies against food antigens in patients with inflammatory bowel disease.

BACKGROUND: Food antigens have been shown to participate in the etiopathogenesis of inflammatory bowel disease (IBD), but their clinical value in IBD is still unclear. AIM: To analyze the levels of specific immunoglobulin G (IgG) and E (IgE) antibodies against food antigens in IBD patients and to determine their clinical value in the pathogenesis of IBD. METHODS: We performed a retrospective study based on patients who visited the First Affiliated Hospital of Nanjing Medical University between August 2016 and January 2018. A total of 137 IBD patients, including 40 patients with ulcerative colitis (UC) and 97 patients with Crohn's disease (CD), and 50 healthy controls (HCs), were recruited. Serum food-specific IgG antibodies were detected by semi-quantitative enzyme-linked immunosorbent assay, and serum food-specific IgE antibodies were measured by Western blot. The value of food-specific IgG antibodies was compared among different groups, and potent factors related to these antibodies were explored by binary logistic regression. RESULTS: Food-specific IgG antibodies were detected in 57.5% of UC patients, in 90.72% of CD patients and in 42% of HCs. A significantly high prevalence and titer of food-specific IgG antibodies were observed in CD patients compared to UC patients and HCs. The number of IgG-positive foods was greater in CD and UC patients than in HCs (CD vs HCs, P = 0.000; UC vs HCs, P = 0.029). The top five food antigens that caused positive specific IgG antibodies in CD patients were tomato (80.68%), corn (69.32%), egg (63.64%), rice (61.36%), and soybean (46.59%). The foods that caused positive specific IgG antibodies in UC patients were egg (60.87%), corn (47.83%), tomato (47.83%), rice (26.09%), and soybean (21.74%). Significantly higher levels of total food-specific IgG were detected in IBD patients treated with anti-TNFα therapy compared to patients receiving steroids and immunosuppressants (anti-TNFα vs steroids, P = 0.000; anti-TNFα vs immunosuppressants, P = 0.000; anti-TNFα vs steroids + immunosuppressants, P = 0.003). A decrease in food-specific IgG levels was detected in IBD patients after receiving anti-TNFα therapy (P = 0.007). Patients who smoked and CD patients were prone to developing serum food-specific IgG antibodies [Smoke: OR (95%CI): 17.6 (1.91-162.26), P = 0.011; CD patients: OR (95%CI): 12.48 (3.45-45.09), P = 0.000]. There was no difference in the prevalence of food-specific IgE antibodies among CD patients (57.1%), UC patients (65.2%) and HCs (60%) (P = 0.831). CONCLUSION: CD patients have a higher prevalence of food-specific IgG antibodies than UC patients and HCs. IBD patients are prone to rice, corn, tomato and soybean intolerance. Smoking may be a risk factor in the occurrence of food-specific IgG antibodies. Food-specific IgG antibodies may be a potential method in the diagnosis and management of food intolerance in IBD.

Fecal microbial dysbiosis in Chinese patients with inflammatory bowel disease.

AIM: To analyze the alterations of fecal microbiota in Chinese patients with inflammatory bowel disease (IBD). METHODS: Fecal samples from 15 patients with Crohn's disease (CD) (11 active CD, 4 inactive CD), 14 patients with active ulcerative colitis (UC) and 13 healthy individuals were collected and subjected to 16S ribosomal DNA (rDNA) gene sequencing. The V4 hypervariable regions of 16S rDNA gene were amplified from all samples and sequenced by the Illumina MiSeq platform. Quality control and operational taxonomic units classification of reads were calculated with QIIME software. Alpha diversity and beta diversity were displayed with R software. RESULTS: Community richness (chao) and microbial structure in both CD and UC were significantly different from those in normal controls. At the phyla level, analysis of the microbial compositions revealed a significantly greater abundance of Proteobacteria in IBD as compared to that in controls. At the genera level, 8 genera in CD and 23 genera in UC (in particular, the Escherichia genus) showed significantly greater abundance as compared to that in normal controls. The relative abundance of Bacteroidetes in the active CD group was markedly lower than that in the inactive CD group. The abundance of Proteobacteria in patients with active CD was nominally higher than that in patients with inactive CD; however, the difference was not statistically significant after correction. Furthermore, the relative abundance of Bacteroidetes showed a negative correlation with the CD activity index scores. CONCLUSION: Our study profiles specific characteristics and microbial dysbiosis in the gut of Chinese patients with IBD. Bacteroidetes may have a negative impact on inflammatory development.

Kv4.3 Modulates the Distribution of hERG.

This study examines the interaction between hERG and Kv4.3. The functional interaction between hERG and Kv4.3, expressed in a heterologous cell line, was studied using patch clamp techniques, western blot, immunofluorescence, and co-immunoprecipitation. Co-expression of Kv4.3 with hERG increased hERG current density (tail current after a step to +10 mV: 26 ± 3 versus 56 ± 7 pA/pF, p < 0.01). Kv4.3 co-expression also increased the protein expression and promoted the membrane localization of hERG. Western blot showed Kv4.3 increased hERG expression by Hsp70. hERG and Kv4.3 co-localized and co-immunoprecipitated in cultured 293 T cells, indicating physical interactions between hERG and Kv4.3 proteins in vitro. In addition, Hsp70 interacted with hERG and Kv4.3 respectively, and formed complexes with hERG and Kv4.3. The α subunit of Ito Kv4.3 can interact with and modify the localization of the α subunit of IKr hERG, thus providing potentially novel insights into the molecular mechanism of the malignant ventricular arrhythmia in heart failure.

Experience of segmentectomy from 36 Chinese patients with non-small cell lung cancer at stage I.

BACKGROUND: Although video-assisted radical operation for lung cancer has been widely accepted for treatment of nonsmall cell lung cancer (NSCLC), the debate over video-assisted thoracic surgery (VATS) segmentectomy still remains. This study analyzed the clinical outcomes using VATS segmentectomy for stage I NSCLC patients to explore the safety and efficacy of VATS segmentectomy for Ia NSCLC. METHODS: Retrospective review was conducted of patients who underwent VATS segmentectomy for clinical stage I NSCLC at Shanghai Chest Hospital between November 2009 and May 2012. VATS segmentectomy was performed on 36 patients. Analyses of the patient group were performed on patient demographics and clinical characteristics, intraoperative parameters, complications, and postoperative survival. RESULTS: Thirty-five of thirty-six patients underwent VATS segmentectomy with only one conversion to open thoracic surgery. There was one peri-operative mortality from the segmentectomy group and all other patients are alive with a median follow up of 327 days. The mean volume of chest tube drainage after operation for segmentectomy was 1021.4 ml. Among other parameters, the mean blood loss was 162.5 ml (50.0 - 1600.0 ml), the mean operation time 124.8 minutes (75.0 - 271.0 minutes), chest tube duration 4.1 days (2 - 8 days), and the mean length of hospital stay 6.2 days (4 - 11 days). There was one (2.8%) locoregional recurrence after segmentectomy. Two patients successfully underwent bilateral segmentectomies and are still disease free. CONCLUSION: For patients with stage I NSCLC, VATS segmentectomy offers a safe and equally effective option and can be applied to complicated operations such as bilateral segmentectomy.

[Effect of Spearmint oil on inflammation, oxidative alteration and Nrf2 expression in lung tissue of COPD rats].

OBJECTIVE: To investigate the effect of Spearmint oil on inflammation, oxidative alteration and Nrf2 expression in rats with chronic obstructive pulmonary disease(COPD). METHODS: COPD model was induced by intratracheal instillation of Klebsiella pneumonia and lipopolysaccharide (LPS) for 12 weeks in rats, and COPD rats were treated with Spearmint oil for 3 weeks. After COPD was induced, the pathological changes, changes in leucocyte number in blood and bronchoalveolar lavage fluid (BALF), MDA in lung homogenate and Nrf2 expression were observed. The effects of Spearmint oil on these changes were determined. RESULT: Spearmint oil 100 mg*kg(-1)significantly reduced leucocyte numbers in BALF, and attenuated bronchiolitis, pulmonary interstitial inflammation and inflammation cell infiltration. Spearmint oil 30-300 mg*kg(-1)decreased the destruction of pulmonary alveolus and the thickness of bronchioles walls, and inhibited goblet cell proliferation. Spearmint oil significantly reduced MDA in lung homogenate, and decreased the expression of Nrf2 protein in lung tissues. CONCLUSION: Spearmint oil has protective effect on lung injury in COPD rats, since it improves pulmonary inflammation,oxidative alteration, and enhances Nrf2 protein expression.