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OBJECTIVES: Intraoperative frozen section (FS) analysis is pivotal in guiding surgical interventions for early-stage lung adenocarcinoma. However, the challenge arises when distinguishing between Minimally Invasive Adenocarcinoma (MIA) and Invasive Adenocarcinoma (IAC) poses diagnostic difficulties. This study investigates the prognosis and clinicopathological characteristics of patients encountering this diagnostic challenge. METHODS: We conducted a retrospective analysis of 7082 intraoperative FSs from early-stage lung adenocarcinoma cases. The cases with pulmonary nodules within 3 cm and diagnosed as indeterminate FSs were included. We analyzed baseline data, computed tomography (CT) findings, and pathological characteristics. Prognostic data were obtained from patients with confirmed IAC diagnoses through final pathological examination. RESULTS: Out of 7082 FSs, 551 cases presented challenges in distinguishing between MIA and IAC. Upon final pathological examination, 233 cases were identified as IAC, while 314 were classified as MIA. The median invasive pathological size in the IAC group was larger than that in the MIA group (0.6 cm vs 0.3 cm). 131 cases (56.2 %) with IAC underwent lobectomy, while 102 cases (43.8 %) underwent sub-lobar resection. Among the MIA cases, 220 cases (69.8 %) underwent sub-lobar resection, while 95 cases (30.2 %) underwent lobectomy. No recurrence and disease specific death was observed during the follow-up period, regardless of surgical strategy. CONCLUSIONS: Indeterminate intraoperative FSs, posing diagnostic challenges in distinguishing between MIA and IAC. Sub-lobar resection presented the same long term survival benefit compared with the lobectomy for indeterminate lung adenocarcinoma within 3 cm during intraoperative FSs.
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As an invasive alien animal, Pomacea canaliculata poses a great danger to the ecology and human beings. Recently, there has been a gradual shift towards bio-friendly control. Based on the development of RNA interference and CRISPR technology as molecular regulatory techniques for pest control, it was determined if the knockout of genes related to sex differentiation in P. canaliculata could induce sterility, thereby helping in population control. However, the knowledge of sex differentiation- and development-related genes in P. canaliculata is currently lacking. Here, transcriptomic approaches were used to study the genes expressed in the two genders of P. canaliculata at various developmental stages. Gonad transcriptomes of immature or mature males and females were compared, revealing 12,063 genes with sex-specific expression, of which 6066 were male- and 5997 were female-specific. Among the latter, 581 and 235 genes were up-regulated in immature and mature females, respectively. The sex-specific expressed genes identified included GnRHR2 and TSSK3 in males and ZAR1 and WNT4 in females. Of the genes, six were involved in reproduction: CCNBLIP1, MND1, DMC1, DLC1, MRE11, and E(sev)2B. Compared to immature snail gonads, the expression of HSP90 and CDK1 was markedly reduced in gonadal. It was hypothesized that the two were associated with the development of females. These findings provided new insights into crucial genetic information on sex differentiation and development in P. canaliculata. Additionally, some candidate genes were explored, which can contribute to future studies on controlling P. canaliculata using molecular regulatory techniques.
Subject(s)
Gene Expression Profiling , Sex Differentiation , Transcriptome , Animals , Sex Differentiation/genetics , Male , Female , Gonads/metabolism , Gonads/growth & development , Gastropoda/genetics , Gastropoda/growth & development , Sexual Development/genetics , Gene Expression Regulation, DevelopmentalABSTRACT
Red swamp crayfish, Procambarus clarkii, is a globally invasive species, which has caused great damage to biodiversity, agriculture, and fishing. Therefore, the development of effective management methods, such as pheromone control, is necessary for biological control and biodiversity protection. However, the components of P. clarkii sex pheromones have not yet been explored, and the chemosensory mechanism of the P. clarkii antennae after stimulation by sex pheromone also remains unknown. In this study, we isolated and identified the candidate bioactive component of the female P. clarkii sex pheromone using ultrafiltration centrifugation, semi-preparative liquid phase separation and omics technologies and conducted bioassays to determine its attraction ability. Meanwhile, RNA-Seq technology was used to analyze the potential chemosensory mechanism of antennae. Our results indicated that the male P. clarkii were uniaxially attracted to the female crude conditioned water (FCW), medium fraction (MF, isolated by ultrafiltration centrifugation), and preparative fragment 6 of females (PFF6, isolated by semi-preparative liquid phase separation). Metabolomic analysis revealed the presence of 18 differential metabolites between the PFF6 and PFM6 samples, among which 15 were significantly upregulated in the PFF6 sample. Bioassay test also showed that mestranol, especially at concentrations of 10-5-10-2 molâl-1, could significantly attract P. clarkii males; therefore, mestranol was identified as the candidate sex pheromone component of P. clarkii females. Furthermore, RNA-Seq results showed that most differentially expressed genes (DEGs) enriched in lipid metabolism and signal transduction pathways were up-regulated in P. clarkii males. In addition, high expressions of Ca2+-binding protein and ion transporting ATPases may enhance the sensitivity of the antennae of P. clarkii males towards sex pheromones. Our study provides data on P. clarkii sex pheromone composition and reveals the molecular mechanism of sex pheromone response in P. clarkii. Moreover, our study provides a referable method for the isolation of candidate bioactive molecules from the P. clarkii sex pheromone.
Subject(s)
Sex Attractants , Female , Male , Animals , Sex Attractants/pharmacology , Astacoidea , Mestranol , Pheromones , Adenosine TriphosphatasesABSTRACT
Background: Patients with rheumatoid arthritis (RA) may be more susceptible to infection by coronavirus disease-19 (COVID-19) due to immune system dysfunction. However, there are still insufficient treatment strategies for patients with RA and COVID-19. Since Jingulian is a traditional Chinese medicine (TCM) with anti-viral and immune regulatory functions, our study aims to explore the detailed mechanisms of Jingulian in treating patients with RA and COVID-19. Methods: All the components of Jingulian were retrieved from pharmacology databases. Then, a series of network pharmacology-based analyses and molecular docking were used to understand the molecular functions, core targets, related pathways, and potential therapeutic targets of Jingulian in patients with RA/COVID-19. Results: A total of 93 genes were identified according to the disease-compound-target network. We investigated that the main targets, signaling pathways, and biological functions of Jingulian in RA and COVID-19. Our results indicated that Jingulian may treat patients with RA/COVID-19 through immune processes and viral processes. Moreover, the results of molecular docking revealed that tormentic acid was one of the top compounds of Jingulian, which had high affinity with Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), and epidermal growth factor receptor (EGFR) in patients with RA/COVID-19. Furthermore, 5 core targets of Jingulian were also identified, including JAK1, Janus kinase 2 (JAK2), STAT3, lymphocyte specific protein tyrosine kinase (LCK), and EGFR. Conclusions: Tormentic acid in Jingulian may regulate JAK1, STAT3, and EGFR, and might play a critical role in RA/COVID-19.
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Background: This study investigated the potential effects of 3-iodothyronamine (T1AM) on myocardial ischemia reperfusion injury (MIRI) and the underlying molecular mechanisms. Methods: A total of 16 adult male Sprague-Dawley rats were randomly divided into 4 groups and administered the following: control [60% dimethyl sulfoxide (DMSO) and 40% saline, pH 7.4], T1AM (25 mg/kg), T1AM (50 mg/kg), or T1AM (100 mg/kg). The rectal temperatures of the rats were measured at different time points. A further 30 adult male Sprague-Dawley rats were randomized and divided into the following 3 groups (n=10 in each group): sham operation, ischemia/reperfusion (I/R), and I/R + T1AM. In the I/R and I/R + T1AM groups, the left anterior descending (LAD) coronary artery of the rats were occluded for 0.5 hour to induce myocardial ischemia, followed by reperfusion for 3 hours in the I/R group. The electrocardiography (ECG), cardiac function, and 2,3,5-triphenyltetrazolium chloride (TTC) staining were examined in rats to evaluate the myocardial injury. The differences in the expression of apoptosis-related and Akt-FoxO1 signaling-related proteins were determined via Western blot. Results: This work verified that T1AM reduced the body temperature of rats in a dose-dependent manner. Additionally, T1AM improved cardiac function and decreased the infarction size caused by MIRI. T1AM reduced the expression of biochemical parameters and apoptosis of myocardial cells. In addition, after treatment with T1AM, the expression of Glut1, pFoxO1 and Akt were reduced, while the expression of FoxO1 and PPARα were increased significantly. Conclusions: Pretreatment of cardiomyocytes with T1AM inhibited apoptosis and protected against ischemia reperfusion injury via the Akt/FoxO1 signaling pathway.
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Purpose: To investigate the detailed mechanism of 3-iodothyronamine (T1AM) in cell apoptosis and programmed necrosis of hypoxia/reoxygenation- (H/R-) induced H9C2 injury. Materials and Methods: Cardiomyocyte H9C2 cells were cultured in vitro for the establishment of cardiomyocyte H/R models. Cells were randomly divided into four groups: the control group, H/R group, T1AM pretreatment group, T1AM pretreatment and H/R (6 µm T1AM+H/R) group. The degree of myocardial injury was determined by the detection of the cardiomyocyte inhibition rate by CCK8 and the detection of lactic dehydrogenase (LDH) activity. Cell apoptosis was assessed through TUNEL assay and flow cytometry analysis. The protein level and mRNA level of RIPK1, RIPK3, and CAMKII were detected by western blotting and qRT-PCR. Results: Compared with the control group, the cell inhibition rate was dramatically elevated in the H/R group. LDH release of cardiomyocytes was significantly increased. Protein and mRNA expressions of RIPK1, RIPK3, and CAMKII were significantly enhanced. Compared with the H/R group, the cell inhibition rate, LDH release, cardiomyocyte necroptosis rate, and protein and mRNA levels of RIPK1, RIPK3, and CAMKII of the T1AM+H/R group were significantly decreased. Conclusion: Pretreatment with T1AM could alleviate cardiomyocytes' H/R injury and inhibit necroptosis of cardiomyocytes, which might exert a protective function upon activation of the RIPK1/RIPK3 pathway.
Subject(s)
Myocytes, Cardiac , Necroptosis , Apoptosis , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Humans , Hypoxia/metabolism , Myocytes, Cardiac/metabolism , RNA, Messenger/metabolism , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , Receptor-Interacting Protein Serine-Threonine Kinases/metabolismABSTRACT
Acute lung injury (ALI) causes high mortality and lacks any pharmacological intervention. Here, we found that pazopanib ameliorated ALI manifestations and reduced mortality in mouse ALI models and reduced edema in human lung transplantation recipients. Pazopanib inhibits mitogen-activated protein kinase kinase kinase 2 (MAP3K2)- and MAP3K3-mediated phosphorylation of NADPH oxidase 2 subunit p47phox at Ser208 to increase reactive oxygen species (ROS) formation in myeloid cells. Genetic inactivation of MAP3K2 and MAP3K3 in myeloid cells or hematopoietic mutation of p47phox Ser208 to alanine attenuated ALI manifestations and abrogates anti-ALI effects of pazopanib. This myeloid MAP3K2/MAP3K3-p47phox pathway acted via paracrine H2O2 to enhance pulmonary vasculature integrity and promote lung epithelial cell survival and proliferation, leading to increased pulmonary barrier function and resistance to ALI. Thus, pazopanib has the potential to be effective for treating ALI.
Subject(s)
Acute Lung Injury , Indazoles/pharmacology , MAP Kinase Kinase Kinase 2/antagonists & inhibitors , MAP Kinase Kinase Kinase 3/antagonists & inhibitors , Pyrimidines/pharmacology , Sulfonamides/pharmacology , Acute Lung Injury/drug therapy , Animals , Humans , Hydrogen Peroxide , Mice , NADPH Oxidases/metabolism , Phosphorylation , Reactive Oxygen SpeciesABSTRACT
BACKGROUNDCurrent clinical management of patients with pulmonary nodules involves either repeated low-dose CT (LDCT)/CT scans or invasive procedures, yet causes significant patient misclassification. An accurate noninvasive test is needed to identify malignant nodules and reduce unnecessary invasive tests.METHODWe developed a diagnostic model based on targeted DNA methylation sequencing of 389 pulmonary nodule patients' plasma samples and then validation in 140 plasma samples independently. We tested the model in different stages and subtypes of pulmonary nodules.RESULTSA 100-feature model was developed and validated for pulmonary nodule diagnosis; the model achieved a receiver operating characteristic curve-AUC (ROC-AUC) of 0.843 on 140 independent validation samples, with an accuracy of 0.800. The performance was well maintained in (a) a 6 to 20 mm size subgroup (n = 100), with a sensitivity of 1.000 and adjusted negative predictive value (NPV) of 1.000 at 10% prevalence; (b) stage I malignancy (n = 90), with a sensitivity of 0.971; (c) different nodule types: solid nodules (n = 78) with a sensitivity of 1.000 and adjusted NPV of 1.000, part-solid nodules (n = 75) with a sensitivity of 0.947 and adjusted NPV of 0.983, and ground-glass nodules (n = 67) with a sensitivity of 0.964 and adjusted NPV of 0.989 at 10% prevalence. This methylation test, called PulmoSeek, outperformed PET-CT and 2 clinical prediction models (Mayo Clinic and Veterans Affairs) in discriminating malignant pulmonary nodules from benign ones.CONCLUSIONThis study suggests that the blood-based DNA methylation model may provide a better test for classifying pulmonary nodules, which could help facilitate the accurate diagnosis of early stage lung cancer from pulmonary nodule patients and guide clinical decisions.FUNDINGThe National Key Research and Development Program of China; Science and Technology Planning Project of Guangdong Province; The National Natural Science Foundation of China National.
Subject(s)
DNA Methylation , DNA, Neoplasm/metabolism , Lung Neoplasms , Multiple Pulmonary Nodules , Tomography, X-Ray Computed , Adult , Aged , Aged, 80 and over , Female , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/metabolism , Male , Middle Aged , Multiple Pulmonary Nodules/diagnosis , Multiple Pulmonary Nodules/diagnostic imaging , Multiple Pulmonary Nodules/metabolism , Retrospective StudiesABSTRACT
OBJECTIVES: The investigation was aimed to evaluate the safety and efficacy of glasses-free 3-dimensional (3D) video-assisted thoracoscopic surgery (VATS) versus 2D VATS for radical resection of non-small cell lung cancer (NSCLC). METHODS: We reviewed the clinical data of patients with pathologically proven NSCLC who underwent glasses-free 3D (the 3D group) and 2D VATS radical lobectomy (the 2D group) with systematic lymph node dissection. The outcomes of this study included operative characteristics and safety of 2D and 3D VATS, and duration of lymphadenectomy of right stations 2 and 4. RESULTS: A total of 190 patients were eligible for the study. The 2D group consisted of 108 patients while the 3D group included 82 patients. The 2 groups were comparable in demographic and baseline variables ( P > .05). The median number of resected lymph nodes was 19 in both groups ( P = .583). The median length of hospital stay was comparable between the 2 groups (2D, 7 days vs 3D, 8 days; P = .167). No operative mortality was reported in either group. Complications developed in 21 (19.4%) patients in the 2D group and 14 (17.1%) in the 3D group ( P = .710). A subgroup analysis of patients who underwent right station 2 and 4 lymphadenectomy showed that the mean time for right station 2 and 4 lymph node dissection was significantly shorter in the 3D group than in the 2D group (3D, 430.9 ± 237.2 vs 2D, 648.6 ± 364.1 seconds; P < .001). CONCLUSIONS: Glasses-free 3D VATS and 2D VATS are comparable in operative characteristics and safety profile for radical resection of NSCLC. Glasses-free 3D visualization facilitates more rapid right-sided mediastinal lymphadenectomy.
Subject(s)
Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/surgery , Thoracic Surgery, Video-Assisted , Aged , Female , Humans , Imaging, Three-Dimensional , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective Studies , Thoracic Surgery, Video-Assisted/adverse effects , Thoracic Surgery, Video-Assisted/methods , Thoracic Surgery, Video-Assisted/statistics & numerical data , Treatment OutcomeABSTRACT
Abuse of synthetic psychostimulants like synthetic cathinones has risen in recent years. 3,4-Methylenedioxypyrovalerone (MDPV) is one such synthetic cathinone that demonstrates a mechanism of action similar to cocaine. Compared to cocaine, MDPV is more potent at blocking dopamine and norepinephrine reuptake and is readily self-administered by rodents. The present study compared the rewarding and reinforcing properties of MDPV and cocaine using systemic injection dose-response and self-administration models. Fifty kilohertz ultrasonic vocalizations (USVs) were recorded as an index of positive affect throughout experiments. In Experiment 1, MDPV and cocaine dose-dependently elicited 50-kHz USVs upon systemic injection, but MDPV increased USVs at greater rates and with greater persistence relative to cocaine. In Experiment 2, latency to begin MDPV self-administration was shorter than latency to begin cocaine self-administration, and self-administered MDPV elicited greater and more persistent rates of 50-kHz USVs versus cocaine. MDPV-elicited 50-kHz USVs were sustained over the course of drug load-up whereas cocaine-elicited USVs waned following initial infusions. Notably, we observed a robust presence of context-elicited 50-kHz USVs from both MDPV and cocaine self-administering rats. Collectively, these data suggest that MDPV has powerfully rewarding and reinforcing effects relative to cocaine at one-tenth doses. Consistent with prior work, we additionally interpret these data in supporting that MDPV has significant abuse risk based on its potency and subjectively positive effects. Future studies will be needed to better refine therapeutic strategies targeted at reducing the rewarding effects of cathinone analogs in efforts to ultimately reduce abuse liability.
Subject(s)
Benzodioxoles/pharmacology , Cocaine/pharmacology , Dopamine Uptake Inhibitors/pharmacology , Pyrrolidines/pharmacology , Reward , Vocalization, Animal/drug effects , Animals , Benzodioxoles/administration & dosage , Cocaine/administration & dosage , Dopamine Uptake Inhibitors/administration & dosage , Male , Pyrrolidines/administration & dosage , Rats , Reinforcement, Psychology , Self Administration , Ultrasonic Waves , Synthetic CathinoneABSTRACT
Nutritional status of 380 hospitalised children aged from 1 month to 5 years with liver disease was evaluated in a single paediatric centre. The total prevalence of stunting (height-for-age Z (HAZ) < -2), underweight (weight-for-age Z (WAZ) < -2) and wasting (weight-for-height Z < -2) was 9·8, 9·0 and 7·9 %, respectively. The overall nutritional risk (-2 ≤ Z < -1) of stunting, underweight and wasting was 11·8, 12·9 and 12·6 %. The prevalence of undernutrition was significantly higher in children with cholestasis than children without cholestasis (stunting, 17·5 %/4·4 %, P < 0·001, and underweight, 14·9 %/4·9 %, P < 0·001). HAZ and WAZ scores were significantly higher in children without cholestasis than children with cholestasis (0·58 (sd 1·59)/-0·68 (sd 1·99), P < 0·001, and 0·37 (sd 1·35)/-0·47 (sd 1·75), P < 0·001). Further multivariate logistic regression analysis strengthened the evidence that cholestasis was significantly associated with undernutrition of stunting (OR = 4·18, P = 0·002) and underweight (OR = 3·26, P = 0·008), and suggested that the prevalence of stunting caused by infection was lower than other aetiologies in hospitalised children with liver disease (OR = 0·10, P = 0·002). We concluded that a high prevalence of malnutrition and risk of undernutrition presents in hospitalised young children with liver disease, especially in children with cholestasis. Nutrition assessment is recommended for hospitalised children with liver disease.
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The push for minimally invasive techniques had led to the development of many surgical tools and the innovation and completion of ever more complex operations. To achieve faster postoperative recovery of patients, we have been dedicated to the development of surgical skills that have allowed us to successfully complete many procedures under video-assisted thoracoscopic surgery (VATS) that are complex even with open approach. Specifically, sleeve, trachea, and carina resections and reconstructions using either general or spontaneous respiration anesthesia (SRA) techniques. Our long term high volume thoracic experience has equipped us with a talented multidisciplinary team with the ability to confidently and safely perform many types of complicated VATS procedures.
ABSTRACT
Mephedrone (4-methylmethcathinone (4-MMC)) (MEPH) is a new psychoactive substance (NPS) of the synthetic cathinone class. MEPH has a chiral center and exists as two enantiomers (R-,S-MEPH), yet stereospecific effects of MEPH have not been extensively investigated in preclinical assays. Because significant behavioral and neurochemical differences can exist between enantiomers, probing effects of stereochemistry on biological activity enables separation of adverse and therapeutic effects. Our prior work showed that R-MEPH, relative to S-MEPH, produced greater locomotor activation, place preference, and facilitation of brain reward thresholds in rodents. The present study sought to determine if MEPH enantiomers display stereospecific reward and reinforcement in rat self-administration assays. In Experiment 1, rats were trained to self-administer racemic MEPH (0.50 mg/kg/inf), and dose substitution effects of R-MEPH (0.50 mg/kg/inf) and S-MEPH (0.25, 0.50, 2.00 mg/kg/inf) were examined. In Experiment 2, separate rats were trained to self-administer R-MEPH (0.25, 0.50, 2.00 mg/kg/inf) or S-MEPH (0.25, 0.50, 2.00 mg/kg/inf) and were thereafter evaluated under progressive-ratio access conditions. Within this cohort, 50 kHz ultrasonic vocalizations (USVs) were recorded to measure potential differences in subjective positive affect associated with MEPH enantiomer self-administration. We identified enantiomer- and dose-dependent effects on infusions earned during self-administration following acquisition of racemic MEPH, with greatest infusions under low-effort, fixed-ratio 1 access conditions from low-dose S-MEPH self-administration. When taxed with progressive-ratio access conditions, rats trained to self-administer R-MEPH showed higher break points than those of rats trained to self-administer S-MEPH. Additionally, R-MEPH elicited greatest rates of 50 kHz USVs compared to S-MEPH. Taken together, these data suggest that the R-enantiomer of MEPH is primarily responsible for the rewarding, reinforcing, and motivational properties of racemic MEPH, which increases our understanding of stereospecific preferences pertaining to MEPH abuse.
Subject(s)
Methamphetamine/analogs & derivatives , Motivation/drug effects , Motivation/physiology , Reward , Animals , Behavior, Animal/drug effects , Behavior, Animal/physiology , Dose-Response Relationship, Drug , Male , Methamphetamine/administration & dosage , Methamphetamine/chemistry , Rats , Rats, Sprague-Dawley , Self Administration , Stereoisomerism , Structure-Activity Relationship , Treatment OutcomeABSTRACT
Tobacco smoking is the leading cause of preventable death in the United States. Nicotine is the principal psychoactive ingredient in tobacco that causes addiction. The structures governing nicotine addiction, including those underlying withdrawal, are still being explored. Nicotine withdrawal is characterized by negative affective and cognitive symptoms that enhance relapse susceptibility, and suppressed dopaminergic transmission from ventral tegmental area (VTA) to target structures underlies behavioral symptoms of nicotine withdrawal. Agonist and partial agonist therapies help 1 in 4 treatment-seeking smokers at one-year post-cessation, and new targets are needed to more effectively aid smokers attempting to quit. Hypothalamic orexin/hypocretin neurons send excitatory projections to dopamine (DA)-producing neurons of VTA and modulate mesoaccumbal DA release. The effects of nicotinic receptor blockade, which is commonly used to precipitate withdrawal, on orexin neurons remain poorly investigated and present an attractive target for intervention. The present study sought to investigate the effects of nicotinic receptor blockade on hypothalamic orexin neurons using mecamylamine to precipitate withdrawal in rats. Separate groups of rats were treated with either chronic nicotine or saline for 7-days at which point effects of mecamylamine or saline on somatic signs and anxiety-like behavior were assessed. Finally, tissue from rats was harvested for immunofluorescent analysis of Fos within orexin neurons. Results demonstrate that nicotinic receptor blockade leads to reduced orexin cell activity, as indicated by lowered Fos-immunoreactivity, and suggest that this underlying cellular activity may be associated with symptoms of nicotine withdrawal as effects were most prominently observed in rats given chronic nicotine. We conclude from this study that orexin transmission becomes suppressed in rats upon nicotinic receptor blockade, and that behavioral symptoms associated with nicotine withdrawal may be aided by intervention upon orexinergic transmission.
Subject(s)
Neurons/drug effects , Nicotinic Antagonists/pharmacology , Orexins/metabolism , Receptors, Nicotinic/drug effects , Animals , Dopamine/pharmacology , Immunohistochemistry/methods , Male , Neurons/metabolism , Nicotine/pharmacology , Oncogene Proteins v-fos/metabolism , Rats, Sprague-Dawley , Ventral Tegmental Area/drug effects , Ventral Tegmental Area/metabolismABSTRACT
The role of video-assisted thoracoscopic surgery (VATS) radical resection in the treatment of lung cancer has widely recognized. Studies have demonstrated that the thoracoscopic radical treatment of lung cancer can achieve similar long-term survival as that of conventional open surgeries; meanwhile, it can be applied for bronchial sleeve resection that is more challenging for most thoracic surgeons. Bronchial sleeve pneumonectomy can avoid total pneumonectomy when removing tumors, and therefore it can lower the surgery-associated mortality and improve the long-term survival by maximizing the preservation of lung function. Thus, it has become a standard procedure for central-type lung cancer. We have completed a glasses-free three-dimensional (3D) complete thoracoscopic surgery in a patient with central-type lung cancer in his right lung. During the surgery, we found the tumor had invaded the right pulmonary trunk, right main bronchus, and lateral wall of superior vena cava.
ABSTRACT
Lung cancer invading the superior vena cava (SVC) is a locally advanced condition, for which poor prognosis is expected with conservative treatment alone. Surgical resection of the lesion can rapidly relieve the symptoms and significantly improve survival for some patients. Replacement, repair and partial resection of SVC via thoracotomy were generally accepted and used in the past. As the rapid development of minimally invasive techniques and devices, partial resection and repair of SVC are feasible via video-assisted thoracic surgery (VATS). However, few studies have reported the VATS surgical techniques. In this study, we reported the crucial techniques of partial resection of SVC via VATS.
ABSTRACT
Lung cancer invading pulmonary trunk is a locally advanced condition, which may indicate poor prognosis. Surgical resection of the lesion can significantly improve survival for some patients. Lobectomy/Pneumonectomy with pulmonary arterioplasty via thoracotomy were generally accepted and used in the past. As the rapid development of minimally invasive techniques and devices, pulmonary arterioplasty is feasible via video-assisted thoracic surgery (VATS). However, few studies have reported the VATS surgical techniques. In this study, we reported the techniques of pulmonary arterioplasty via VATS.
ABSTRACT
BACKGROUND: Three-dimensional (3D) vision systems are now available for thoracic surgery. It is unclear whether 3D video-assisted thoracic surgery (VATS) is superior to 2D VATS systems. This study aimed to compare the operative and perioperative data between 2D and 3D VATS lobectomy (VTL) and to identify the actual role of 3D VTL in thoracic surgery. METHODS: A two-institutional comparative study was conducted from November 2013 to November 2014 at Liaoning Cancer Hospital & Institute and the First Affiliated Hospital of Guangzhou Medical University, China, of 300 patients with resectable non-small cell lung cancer (NSCLC). Patients were assigned to receive either the 3D VATS (n=150) or 2D VATS (n=150) lobectomy. The operative and perioperative data between 2D VATS and 3D VATS were compared. RESULTS: Although there was no significant difference between the two groups regarding the incidence of each single complication, a significantly less operative time was found in the 3D VATS group (145 min) than in the 2D VATS group (176 min) (P=0.006). Postoperative mortality rates in 3D VATS and 2D VATS groups were both 0%.No significant difference was found between groups for estimated blood loss (P=0.893), chest drainage tube placement time (P=0.397), length of hospital stay (P=0.199), number of lymph nodes resected (P=0.397), postoperative complications (P=0.882) and cost of care (P=0.913). CONCLUSIONS: Early results of this study demonstrate that the 3D VATS lobectomy procedure can be performed with less operative time. 3D VATS and 2D VATS lobectomy are both safe procedures in first-line surgical treatment of NSCLC.
ABSTRACT
In the present paper we describe our on-going project investigating the functional roles of the N-methyl-D-aspartate (NMDA) receptor subunit NR3A. We find that NR3A mRNA is abundant both in embryonic and adult human brain, in contrast to the almost non-existing expression in adult rodent brain. Human NR3A (hNR3A) protein expression is particularly abundant in the cerebral cortex, as shown by western blot using NR3A-specific antibodies. Distribution of hNR3A in adult human brain shows a similar pattern as NR3A in post-natal rodent brain. We have previously reported that NR3A contains a glycine binding site, with similar affinity as the glycine binding site of NR1 subunits. This suggests that NR3A may replace one of the two NR1 subunits in native NMDA receptors. Cloning of hNR3A showed a human-specific polyproline-sequence in the intracellular C-terminus, that may bind to SH3-domains. We hypothesized that the significant differences in expression in the adult human and rodent brain could be due to an atypical interaction of hNR3A with the SH3 domain of the synaptic scaffolding protein PSD-95, that binds to NR2 subunits through its PDZ domains. However, using a number of different protein interaction assays, binding of PSD-95 to hNR3A could no be demonstrated either in vitro or in vivo. To identify intracellular signaling pathways for NR3A-containing NMDA receptors, we screened for proteins interacting with hNR3A and identified three proteins: plectin, CARP-1 and GPS2. The possible physiological roles of these interactions are discussed.
Subject(s)
Gene Expression Regulation, Developmental/physiology , Receptors, N-Methyl-D-Aspartate/physiology , Synapses/physiology , Animals , Cerebral Cortex/cytology , Cerebral Cortex/physiology , Dendritic Spines/physiology , Humans , Mice , Protein Subunits , Rats , Receptors, N-Methyl-D-Aspartate/geneticsABSTRACT
We investigated the ability of GM1 to induce phosphorylation/activation of the extracellular-regulated protein kinases (ERKs) in the striatum, hippocampus and frontal cortex of aged male Sprague-Dawley rats. Three different treatment paradigms were used: a single application of GM1 to brain slices in situ, a single intracerebroventricular (icv) administration of GM1 in vivo, and chronic administration of GM1 in vivo. In situ, GM1 induced a rapid and transient activation of ERK1 and ERK 2 in both young and aged rats, and a similar effect was observed after stimulation with the neurotrophins NGF and BDNF. The aged brain appeared to respond more robustly to neurotrophic stimulation with the pERK2 response being significantly greater in the hippocampus and frontal cortex. Acute icv administration of GM1 resulted in short-lasting phosphorylation of ERKs in both aged groups, while chronic administration of GM1 induced a protracted phosphorylation of ERKs. Following chronic GM1 treatment, pERK2 levels in the aged hippocampus were elevated over young control animals. In agreement with reports that GM1 phosphorylates TrkA in vitro or in situ, treatment with GM1 increased the phosphorylation of TrkA in hippocampus of both young and aged animals. These observations indicate that the aged brain maintains the ability to respond to neurotrophic stimuli and put forward the proposition that the ERK cascade is associated with the action(s) of GM1 ganglioside in vivo.