Bridging childhood to adulthood: the impact of early life stress on acute stress responses.

Background: Childhood trauma exerts enduring impacts on the physical and psychological well-being of individuals in adulthood, influencing their daily functioning. This study aims to investigate the impact of childhood trauma on stress recovery in adults, concentrating on heart rate variations during acute stress exposure. Methods: A cohort of 126 participants completed the Childhood Trauma Questionnaire (CTQ) and underwent the Trier Social Stress Test (TSST) to elicit acute stress, with continuous heart rate (HR) monitoring for stress recovery assessment. Results: The results revealed a negative correlation between childhood trauma and stress recovery, prominently observed in instances of emotional neglect and abuse. Individuals with heightened childhood trauma exhibited protracted stress recovery following acute stress exposure. Conclusion: Childhood traumatic experiences were associated with the recovery from acute stress, as indicated by heart rate indices. These findings contribute to the foundational framework for psychological interventions tailored to individuals with a history of childhood trauma.

Biallelic variants in the COQ4 gene caused hereditary spastic paraplegia predominant phenotype.

INTRODUCTION: Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders characterized by progressive degeneration of upper motor neurons. Homozygous or compound heterozygous variants in COQ4 have been reported to cause primary CoQ10 deficiency-7 (COQ10D7), which is a mitochondrial disease. AIMS: We aimed to screened COQ4 variants in a cohort of HSP patients. METHODS: A total of 87 genetically unidentified HSP index patients and their available family members were recruited. Whole exome sequencing (WES) was performed in all probands. Functional studies were performed to identify the pathogenicity of those uncertain significance variants. RESULTS: In this study, five different COQ4 variants were identified in three Chinese HSP pedigrees and two variants were novel, c.87dupT (p.Arg30*), c.304C>T (p.Arg102Cys). More importantly, we firstly described two early-onset pure HSP caused by COQ4 variants. Functional studies in patient-derived fibroblast lines revealed a reduction cellular CoQ10 levels and the abnormal mitochondrial structure. CONCLUSIONS: Our findings revealed that bilateral variants in the COQ4 gene caused HSP predominant phenotype, expanding the phenotypic spectrum of the COQ4-related disorders.

[Analgesic effect of buccal acupuncture on patients after lumbar spinal fusion: a randomized controlled trial].

OBJECTIVE: To observe the effect of buccal acupuncture on pain after lumbar spinal fusion. METHODS: Sixty patients undergoing lumbar spinal fusion were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 1 case was eliminated). The patients in the control group were treated with routine anesthesia. On the basis of the control group, the patients in the observation group were treated with buccal acupuncture at bilateral back point, waist point, and sacral point for 30 min per treatment. The first acupuncture was given before anesthesia induction, and then once a day postoperation for two days, totally 3 treatments. The dosage of sufentanil, the number of remedial analgesia, and the incidence of nausea and vomiting within 48 h after surgery were compared between the two groups; rest and motion visual analogue scale (VAS) scores at 2 (T1), 8 (T2), 12 (T3), 24 (T4), and 48 (T5) h after surgery were observed; the quality of recovery-15 scale (QoR-15) at 24 and 48 h after surgery were evaluated. RESULTS: The dosage of sufentanil and the number of remedial analgesia within 48 h after surgery in the observation group were lower than those in the control group (P<0.01). There was no significant statistically difference in rest and motion VAS scores between the two groups in T1, T2, T3, T4 and T5 (P>0.05). The QoR-15 scores in the observation group at 24 and 48 h after surgery were higher than those in the control group (P<0.01). The incidence of nausea in the observation group was lower than that in the control group (P<0.05). CONCLUSION: Buccal acupuncture could reduce the amount of postoperative analgesic drugs of patients after lumbar spinal fusion, and promote early postoperative recovery.

Clinical feature difference between juvenile amyotrophic lateral sclerosis with SPTLC1 and FUS mutations.

BACKGROUND: Juvenile amyotrophic lateral sclerosis (JALS) is an uncommon form of amyotrophic lateral sclerosis whose age at onset (AAO) is defined as prior to 25 years. FUS mutations are the most common cause of JALS. SPTLC1 was recently identified as a disease-causative gene for JALS, which has rarely been reported in Asian populations. Little is known regarding the difference in clinical features between JALS patients carrying FUS and SPTLC1 mutations. This study aimed to screen mutations in JALS patients and to compare the clinical features between JALS patients with FUS and SPTLC1 mutations. METHODS: Sixteen JALS patients were enrolled, including three newly recruited patients between July 2015 and August 2018 from the Second Affiliated Hospital, Zhejiang University School of Medicine. Mutations were screened by whole-exome sequencing. In addition, clinical features such as AAO, onset site and disease duration were extracted and compared between JALS patients carrying FUS and SPTLC1 mutations through a literature review. RESULTS: A novel and de novo SPTLC1 mutation (c.58G>A, p.A20T) was identified in a sporadic patient. Among 16 JALS patients, 7/16 carried FUS mutations and 5/16 carried respective SPTLC1 , SETX , NEFH , DCTN1 , and TARDBP mutations. Compared with FUS mutation patients, those with SPTLC1 mutations had an earlier AAO (7.9 ±â€Š4.6 years vs. 18.1 ±â€Š3.9 years, P  < 0.01), much longer disease duration (512.0 [416.7-607.3] months vs. 33.4 [21.6-45.1] months, P  < 0.01), and no onset of bulbar. CONCLUSION: Our findings expand the genetic and phenotypic spectrum of JALS and help to better understand the genotype-phenotype correlation of JALS.

Impaired Cell Cycle Progression and Self-Renewal of Fetal Neural Stem and Progenitor Cells in a Murine Model of Intrauterine Growth Restriction.

Individuals with intrauterine growth restriction (IUGR) are at an increased risk for neurodevelopmental impairment. Fetal cortical neurogenesis is a time-sensitive process in which fetal neural stem cells (NSCs) follow a distinct pattern of layer-specific neuron generation to populate the cerebral cortex. Here, we used a murine maternal hypoxia-induced IUGR model to study the impact of IUGR on fetal NSC development. In this model, timed-pregnant mice were exposed to hypoxia during the active stage of neurogenesis, followed by fetal brain collection and analysis. In the IUGR fetal brains, we found a significant reduction in cerebral cortical thickness accompanied by decreases in layer-specific neurons. Using EdU labeling, we demonstrated that cell cycle progression of fetal NSCs was delayed, primarily observed in the G2/M phase during inward interkinetic nuclear migration. Following relief from maternal hypoxia exposure, the remaining fetal NSCs re-established their neurogenic ability and resumed production of layer-specific neurons. Surprisingly, the newly generated neurons matched their control counterparts in layer-specific marker expression, suggesting preservation of the fetal NSC temporal identity despite IUGR effects. As expected, the absolute number of neurons generated in the IUGR group remained lower compared to that in the control group due to a reduced fetal NSC pool size as a result of cell cycle defect. Transcriptome analysis identified genes related to energy expenditure and G2/M cell cycle progression being affected by maternal hypoxia-induced IUGR. Taken together, maternal hypoxia-induced IUGR is associated with a defect in cell cycle progression of fetal NSCs, and has a long-term impact on offspring cognitive development.

SOD1 Mutation Spectrum and Natural History of ALS Patients in a 15-Year Cohort in Southeastern China.

Background: Mutations in superoxide dismutase 1 gene (SOD1) are the most frequent high penetrant genetic cause for amyotrophic lateral sclerosis (ALS) in the Chinese population. A detailed natural history of SOD1-mutated ALS patients will provide key information for ongoing genetic clinical trials. Methods: We screened for SOD1 mutations using whole exome sequencing (WES) in Chinese ALS cases from 2017 to 2021. Functional studies were then performed to confirm the pathogenicity of novel variants. In addition, we enrolled previously reported SOD1 mutations in our centers from 2007 to 2017. The SOD1 mutation spectrum, age at onset (AAO), diagnostic delay, and survival duration were analyzed. Results: We found two novel SOD1 variants (p.G17H and p.E134*) that exerted both gain-of-function and loss-of-function effects in vitro. Combined with our previous SOD1-mutated patients, 32 probands with 21 SOD1 mutations were included with the four most frequently occurring mutations of p.V48A, p.H47R, p.C112Y, and p.G148D. SOD1 mutations account for 58.9% of familial ALS (FALS) cases. The mean (SD) AAO was 46 ± 11.4 years with a significant difference between patients carrying mutations in exon 1 [n = 5, 34.6 (12.4) years] and exon 2 [n = 8, 51.4 (8.2) years] (p = 0.038). The mean of the diagnostic delay of FALS patients is significantly earlier than the sporadic ALS (SALS) patients [9.5 (4.8) vs. 20.3 (9.3) years, p = 0.0026]. In addition, male patients survived longer than female patients (40 vs. 16 months, p = 0.05). Conclusion: Our results expanded the spectrum of SOD1 mutations, highlighted the mutation distribution, and summarized the natural history of SOD1-mutated patients in southeastern China. Male patients were found to have better survival, and FALS patients received an earlier diagnosis. Our findings assist in providing a detailed clinical picture, which is important for ongoing genetic clinical trials.

Males with low risk-taking propensity overestimate risk under acute psychological stress.

Arousing research has investigated stressed individuals' decision biases, but whether and how stress and individual traits interact to impact the underlying decision-making process is unknown. Here, we aim to explore the effect of acute stress on the interaction between the objective level of risk and subjective risk preference (i.e. risk-taking propensity). Eighty-three healthy males participated in the study. We adopted the Trier Social Stress Test (TSST) to induce acute psychological stress and categorized participants into the high or low risk-taking propensity (HRP/LRP) group according to their traits in daily life. The Balloon Analogue Risk Task (BART) was applied to measure their feedback processing in a risky decision task, while behavioral indexes and EEG signals were recorded. The results showed that stressful participants pumped fewer times than the controls, especially for the LRP under stress, indicating that they were more willing to avoid taking risks. Compared with the stressed HRP group, the stressed LRP showed higher salivary cortisol responses and a more positive FRN following positive feedback in higher risk levels. It implies that acute psychological stress leads the LRP to overestimate the risk probability and become more cautious in the sequential processing of risk. These findings highlight the role of the feedback process and individual traits in risky decision-making under stress.

Quantifying Fetal Reprogramming for Biomarker Development in the Era of High-Throughput Sequencing.

Gestational hypertensive disorders continue to threaten the well-being of pregnant women and their offspring. The only current definitive treatment for gestational hypertensive disorders is delivery of the fetus. The optimal timing of delivery remains controversial. Currently, the available clinical tools do not allow for assessment of fetal stress in its early stages. Placental insufficiency and fetal growth restriction secondary to gestational hypertensive disorders have been shown to have long-term impacts on offspring health even into their adulthood, becoming one of the major focuses of research in the field of developmental origins of health and disease. Fetal reprogramming was introduced to describe the long-lasting effects of the toxic intrauterine environment on the growing fetus. With the advent of high-throughput sequencing, there have been major advances in research attempting to quantify fetal reprogramming. Moreover, genes that are found to be differentially expressed as a result of fetal reprogramming show promise in the development of transcriptional biomarkers for clinical use in detecting fetal response to placental insufficiency. In this review, we will review key pathophysiology in the development of placental insufficiency, existing literature on high-throughput sequencing in the study of fetal reprogramming, and considerations regarding research design from our own experience.

SNPs within microRNA binding sites and the prognosis of breast cancer.

Single nucleotide polymorphisms (SNPs) within microRNA binding sites can affect the binding of microRNA to mRNA and regulate gene expression, thereby contributing to cancer prognosis. Here we performed a two-stage study of 2647 breast cancer patients to explore the association between SNPs within microRNA binding sites and breast cancer prognosis. In stage I, we genotyped 192 SNPs within microRNA binding sites using the Illumina Goldengate platform. In stage II, we validated SNPs associated with breast cancer prognosis in another dataset using the TaqMan platform. We identified 8 SNPs significantly associated with breast cancer prognosis in stage I (P<0.05), and only rs10878441 was statistically significant in stage II (AA vs CC, HR=2.21, 95% CI: 1.11-4.42, P=0.024). We combined the data from stage I and stage II, and found that, compared with rs10878441 AA genotype, CC genotype was associated with poor survival of breast cancer (HR=2.19, 95% CI: 1.30-3.70, P=0.003). Stratified analyses demonstrated that rs10878441 was related to breast cancer prognosis in grade II and lymph node-negative patients (P<0.05). The Leucine-rich repeat kinase 2 (LRRK2) rs10878441 CC genotype is associated with poor prognosis of breast cancer in a Chinese population and may be used as a potential prognostic biomarker for breast cancer. • The LRRK2 rs10878441 CC genotype is associated with poor prognosis of breast cancer in a Chinese population. • Stratified analyses demonstrated that rs10878441 was related to breast cancer prognosis in grade II patients and lymph node-negative patients.

The SLC25A42 Transcript Is a Biomarker for Fetal Reprogramming in Response to Placental Insufficiency in Preterm Newborns Under 32 Weeks Gestation-A Pilot Study.

Introduction: Timing of medical delivery of preterm newborns exposed to placental insufficiency is largely determined by umbilical artery blood flow and maternal clinical manifestations. There is a lack of tools to properly assess fetal body response to placental insufficiency before or upon delivery. Yet, short- and long-term comorbidities associated with placental insufficiency and the consequential intrauterine growth restriction may be a result of fetal response following prolonged stress. This study aims to establish a procedure to investigate fetal/neonatal transcriptional response to placental insufficiency as part of an initiative to identify cost-effective biomarkers for assessing fetal response to placental insufficiency. Methods: A prospective pilot study involving newborns with birth gestation <32 weeks was conducted to compare gene expression profiles in whole blood collected at birth among three clinically distinct groups - preeclampsia without placental insufficiency (PE), placental insufficiency (PI), and non-PE/PI groups. Results: Whole blood from 11, 3, and 6 newborns in the non-PE/PI, PE, and PI groups were obtained. A transcriptome analysis found that the majority of the genes were downregulated in the PI group, suggesting global transcriptional inactivation. Intriguingly, SLC25A42, which encodes a mitochondrial transporter for coenzyme A and adenosine-3',5'-diphosphate, was significantly upregulated in the PI group. Conclusion: Transcriptional biomarkers for assessing fetal response to placental insufficiency may provide a useful tool to better understand the pathophysiology of fetal reprogramming in response to placental insufficiency. The validity and the role of SLC25A42, as well as its correlation with short- and long-term neonatal outcomes, warrants further investigation.

Perceived control moderates the impact of academic stress on the attention process of working memory in male college students.

Academic stress is a common long-term stress among the student population and is known to impact working memory within the frontoparietal attention network. Perceived control is an individual variation that may play a buffering role between stress and overall adjustment. In this study, we addressed the moderating effects of perceived control between academic stress and working memory. Fifty-nine male college students participated in the study. Academic stress and perceived control were assessed before participants completed a working memory (n-back) task. Event-related potentials (ERPs) including P2 and P3 were analyzed to examine the attention and maintenance processes of working memory. A moderating effect of perceived control on the relationship between academic stress and working memory was found. For students with low levels of perceived control, academic stress was negatively associated with P2 amplitudes at the high workload (3-back) task, suggesting a negative impact on attention process of working memory. In contrast, academic stress did not affect students with high and moderate levels of perceived control. The results indicate that perceived control may serve as a buffer to protect the cognitive function from the disruption of academic stress.

A Nomogram To Predict The Overall Survival Of Breast Cancer Patients And Guide The Postoperative Adjuvant Chemotherapy In China.

PURPOSE: We aim to construct a nomogram to predict breast cancer survival and guide postoperative adjuvant chemotherapy in China. PATIENTS AND METHODS: A total of 5,504 breast cancer patients from the Tianjin Breast Cancer Cases Cohort were included. Multivariable Cox regression was used to investigate the factors associated with overall survival (OS) and a nomogram was constructed based on these prognostic factors. The nomogram was internal and external validated and the performance was evaluated by area under the curve (AUC) and calibration curve. The partial score was also constructed and stratified them into low, moderate and high-risk subgroups for death according to the tripartite grouping method. Multivariate Cox regression analysis and the propensity score matching method were respectively used to test the association between adjuvant chemotherapy and OS in different risk subgroups. RESULTS: Age, diameter, histological differentiation, lymph node metastasis, estrogen, and progesterone receptor were incorporated into the nomogram and validation results showed this nomogram was well-calibrated to predict the 3-year [AUC =74.1%; 95% confidence interval (CI): 70.1-78.0%] and 5-year overall survival [AUC =72.3%; 95% CI: 69.6-75.1%]. Adjuvant chemotherapy was negatively associated with death in high risk subgroup [Hazard Ratio (HR) = 0.54; 95% CI: 0.37-0.77; P<0.001]. However, no significant association were found in groups with low (HR=1.47; 95% CI: 0.52-4.19; P=0.47) and moderate risk (HR=0.78; 95% CI: 0.42-1.48; P=0.45). The 1:1 PSM generated 822 pairs of well-matched patients and Kaplan-Meier showed the high-risk patients could benefit from chemotherapy, whereas low risk and moderate risk subjects did not appear to benefit from chemotherapy. CONCLUSION: Not all of the breast cancer patients benefit equally from chemotherapy. The nomogram could be used to evaluate the overall survival of breast cancer patients and predict the magnitude of benefit and guide adjuvant chemotherapy for breast cancer patients after surgery.

Age at menarche and epithelial ovarian cancer risk: A meta-analysis and Mendelian randomization study.

Age at menarche (AAM) was found to be associated with ovarian cancer risk in previous observational studies. However, the causality of this association remains unclear. Here, after systematic meta-analyses, we performed two-sample Mendelian randomization (MR) analyses to evaluate the causal effect of AAM in epithelial ovarian cancer (EOC) etiology. We performed meta-analyses including 11 410 cases and 1 163 117 noncases to quantitatively evaluate the association between AAM and ovarian cancer risk. In MR analyses, we used 25 single nucleotide polymorphisms (SNPs) associated with AAM for Chinese and 390 SNPs for Europeans as instrumental variables. MR estimates were calculated using inverse-variance weighted methods from 1044 cases and 1172 controls in a Chinese genome-wide association study and validated by the Ovarian Cancer Association Consortium and Consortium of Investigators of Modifiers of BRCA1/2 studies with 29 396 cases and 68 502 controls of European ancestry. In meta-analyses, we observed an inverse association (odds ratio [OR] = 0.96, 95% confidence interval [CI] = 0.93 to 1.00, P = 0.036) between per year older AAM and ovarian cancer risk in case-control studies, but no association was observed in cohort studies. In MR analyses, the OR of EOC risk per year increase in AAM was 0.81 (95% CI = 0.67 to 0.97, P = 0.026) in Chinese and 0.94 (95% CI = 0.90 to 0.98, P = 0.003) in Europeans, respectively. Our study supports a causal association between AAM and EOC risk.

Comparison of breast cancer risk factors among molecular subtypes: A case-only study.

Epidemiological studies have a clear definition of the risk factors for breast cancer. However, it is unknown whether the distribution of these factors differs among breast cancer subtypes. We conducted a hospital-based case-only study consisting of 8067 breast cancer patients basing on the Tianjin Cohort of Breast Cancer Cases. Major breast cancer subtypes including luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched and basal-like were defined by estrogen receptor, progesterone receptor, HER2, and Ki-67 status. Variables including demographic characteristics, reproductive factors, lifestyle habits, imaging examination, and clinicopathologic data were collected for patients. Chi-square test and one-way analysis of variance were used to compare the distributions of variables among the four breast cancer subtypes. Multivariate logistic regression was used to estimate the odds ratios and associated 95% confidence intervals where luminal A patients served as the reference group. Overall, more commonality rather than heterogeneity on the distributions of factors was found between the four molecular subtypes of breast cancer. The proportion of overweight and obesity were lower in HER2-enriched subtype. Women with age at menarche ≤13 years were more likely to be found in basal-like subtype. Postmenopausal women were more frequent in HER2-enriched and basal-like subtypes. Women with benign breast disease and higher breast density were more common in HER2-enriched subtype. Risk factor scoring showed that total risk scores were similar among the four subtypes. HER2-enriched and basal-like subtypes were more frequently diagnosed with large tumors. Calcification was more likely to be found in luminal B and HER2-enriched subtypes, whereas less distributed in basal-like subtype. Most of the breast cancer risk factors were similarly distributed among the four major breast cancer subtypes; commonality is predominant.

Live-cell Migration Assays to Study Motility of Neural andGlial (Oligodendrocyte) Progenitor Cells.

Cell motility has been extensively studied in in vitro models using fibroblasts and keratocytes, but the cell type-specific mechanisms underlying migration of lineage- or disease-specific cells, such as neural and glial progenitor cells, remain an active field for investigation. The migrating neural and glial progenitor cells contribute to the development, tissue repair and tumor invasion in the central nervous system (CNS). Cell migration is a highly dynamic process which relies on membranous protrusions to assemble, extend, disassemble and retract. In the CNS, the motility of neural and glial progenitor cells is affected by various cell-autonomous and non-cell-autonomous mechanisms such as signaling molecules, actin and microtubule interactions, and environmental cues. Here, we described a live-cell migration assay for use in the assessment of neural and glial progenitor cell migration. We first will demonstrate the procedures for isolating and culturing neural and glial progenitor cells. Next, we will demonstrate the acquisition of time-lapse images using phase contrast microscopy, the methods for quantification and the analyses of various motility parameters including speed, velocity, straightness and leading-edge dynamics. This method allows researchers to dissect the mechanisms of cell motility in response to different environmental cues, such as chemoattractive and repulsive signals, matrix adhesiveness and stiffness. This assay also allows researchers to study migration of pharmacologically and genetically manipulated cells.

Clinical effect of off-pump coronary artery bypass grafting for the patients over 70 years with coronary artery disease / 中国胸心血管外科临床杂志

@#Objective     To evaluate the clinical efficacy of coronary artery bypass grafting in the treatment of coronary artery disease patients aged over 70 years. Methods     A total of 160 patients with coronary atherosclerotic heart disease underwent off-pump coronary artery bypass grafting from January 2013 to December 2017. There were 94 males and 66 females at age of 70–85 (76.67±2.33) years. Operations were performed by using sternal median incision with the assistance of local myocardial surface fixator and shunt plug, and the saphenous vein and internal mammary arterywere used as grafted vessels. Results     All the patients were received successful off-pump coronary artery bypass grafting without death, and the cardiac function improved significantly. There were 62 patients with the internal mammary artery bridge and 98 patients with the whole vein bridge. All the patients were followed-up for 1 to 4 years. All the patients had obvious relief of angina pectoris. Conclusion     Off-pump coronary artery bypass grafting for the treatment of elderly patients with coronary heart disease is an effective and safe operation, especially for patients with renal insufficiency, cerebrovascular disease, respiratory disease and severe left ventricular dysfunction.

Neuronal Precursor Migration in Ex Vivo Brain Slice Culture.

Neuronal migration during fetal brain development is a well-coordinated process between the migrating neurons and their substrates, the basal processes of the radial glial cells (RGCs). The progeny-progenitor relationship between the migrating neurons and the RGCs in the developing fetal brain may make interpretations of the results difficult, because the variable in question may affect both the RGCs and the migrating neurons in different ways. A transplantation assay combining migrating cells and the scaffolding tissue from two different sources may circumvent this issue. We developed an ex vivo brain slice transplantation assay that allows recording of migrating neurons in real time.

Applications of nerve stimulator-guided thoracic paravertebral nerve block plus general anesthesia in small-incision lung cancer surgery.

OBJECTIVE: The aim of the study was to investigate the application of nerve stimulator-guided thoracic paravertebral nerve block (TPVB) plus general anesthesia (GA) in small-incision lung cancer surgery. METHODS: Forty patients scheduled for small-incision lung cancer surgery, the American Society of Anesthesiologists Grade I-II, were randomized into a TPVB-GA group (Group P) and a GA group (Group G), with 20 cases in each group. The dosage of general anesthetic, mean arterial pressure (MAP) at each time point, and heart rate (HR) of the two groups were recorded. The postoperative respiration recovery time, extubation time, incidence of adverse reactions, and postoperative visual analog scale (VAS) scores of the two groups were also observed. RESULTS: Group P showed stable hemodynamics, and lower MAP and HR at each time point than Group G (P < 0.05). The intraoperative dosage of general anesthetic in Group P was lower than that in Group G (P < 0.05). The respiration recovery time and extubation time in Group P were significantly shorter than those in Group G (P < 0.05); the incidence of agitation was significantly lower than that in Group G (P < 0.05). The VAS scores of Group P under quiet and cough status were also better than Group G (P < 0.05). CONCLUSIONS: Nerve stimulator-guided TPVB-GA is suitable for small-incision lung cancer surgery.