1,7-Bis(4-hydroxyphenyl)-1,4-heptadien-3-one induces lung cancer cell apoptosis via the PI3K/Akt and ERK1/2 pathways.

1,7-Bis(4-hydroxyphenyl)-1,4-heptadien-3-one (EB30) is a diarylheptanoid-like compound isolated from Viscum coloratum. This curcumin analog exhibits significant cytotoxic activity against HeLa, SGC-7901, and MCF-7 cells. However, little is known about the anticancer effects and mechanisms of EB30 in human lung cancer. The current study reports that EB30 significantly reduced the cell viability of A549 and NCI-H292 human lung cancer cells. Further examination revealed that EB30 not only induced cell cycle arrest and promoted the generation of reactive oxygen species (ROS) but also induced cell apoptosis through the intrinsic and extrinsic signaling pathways. Furthermore, EB30 upregulated the expression levels of p-ERK1/2 and p-P90RSK, whereas downregulating the phosphorylation of Akt and P70RSK. Cell viability was further inhibited by the combination of EB30 with LY294002 (a specific PI3K inhibitor) or U0126 (a MEK inhibitor). The current study indicates that EB30 is a potential anticancer agent that induces cell apoptosis via suppression of the PI3K/Akt pathway and activation of the ERK1/2 pathway.

Synthesis of difluoromethylated enynes by the reaction of α-(trifluoromethyl)styrenes with terminal alkynes.

A novel and efficient method for the synthesis of difluoromethylated enynes by the reaction of α-(trifluoromethyl)styrenes with terminal alkynes with the assistance of NaOtBu was described. The mechanism of the reaction might involve the SN2' reaction of α-(trifluoromethyl)styrenes and a subsequent 1,3-H shift. Isomerization (E → Z) of 1-difluoromethyl-1,3-enynes in the presence of ZrCl4 was also developed.

Synthesis of N,N-disubstituted 2-aminothiophenes by the cyclization of gem-difluoroalkenes with ß-keto thioamides.

A novel and effective method for the construction of highly functionalized aminothiophenes via the cyclization of gem-difluoroalkenes with ß-keto tertiary thioamides is described. The reactions proceed smoothly with the assistance of K2CO3 under transition-metal-free conditions, affording a variety of valuable N,N-disubstituted 2-aminothiophenes in moderate to good yields.

[Clinical Efficacy Analysis of Wedge Resection of Pulmonary 
in Patients with Small Volume Invasive Lung Adenocarcinoma].

BACKGROUND: With further understanding and research into non-small cell lung cancer with tumours ≤2 cm in maximum diameter, segmental lung resection is able to achieve the same long-term prognosis as lobectomy. However, there are few studies on the prognostic effect of wedge resection on small volume invasive lung adenocarcinoma with an invasion depth of 0.5 to 1.0 cm. Therefore, this study focuses on the clinical efficacy and prognosis of wedge resection in patients with small-volume invasive lung adenocarcinoma. METHODS: A retrospective analysis of the medical records of 208 patients who underwent surgery in the Department of Thoracic Surgery of the Affiliated Provincial Hospital of Anhui Medical University from February 2016 to December 2017 was made, and the postoperative pathological results confirmed small volume invasive lung adenocarcinoma. According to their surgical methods, they were divided into lobectomy group (n=115), segmentectomy group (n=48) and wedge resection group (n=45). Kaplan-Meier survival curve estimation and Cox proportional risk regression model were used to explore the influence of different surgical methods on the prognosis of patients with small volume invasive lung adenocarcinoma. RESULTS: The wedge resection group had better perioperative outcomes compared with the segmentectomy group and lobectomy group, with statistically significant differences in intraoperative bleeding (P=0.036), postoperative drainage (P<0.001), operative time (P=0.018), postoperative time with tubes (P=0.001), and postoperative complication rate (P=0.006). There were no significant differences when comparing the three groups in terms of survival rate (lobectomy group vs segmentectomy group, P=0.303; lobectomy group vs wedge resection group, P=0.742; and segmentectomy group vs wedge resection group, P=0.278) and recurrence-free survival rate (lobectomy group vs segmentectomy group, P=0.495; lobectomy group vs wedge resection group, P=0.362; segmentectomy group vs wedge resection group, P=0.775). Univariate and multivariate survival analyses showed that consolidation tumor ratio (CTR) was the prognostic factor of overall survival and revurrence-free survival for patients with small-volume invasive lung adenocarcinoma (P<0.05). CONCLUSIONS: Wedge resection in patients with small volume invasive lung adenocarcinoma can achieve long-term outcomes similar to segmentectomy and lobectomy. When the CTR≤0.5, wedge resection is preferred in such patients.

[Effect of Preserving the Pulmonary Branch of Vagus Nerve on Postoperative Cough 
in Patients with Stage I Peripheral Lung Adenocarcinoma].

BACKGROUND: Cough is one of the main complications after pulmonary surgery, which seriously affects the postoperative quality of life. Preserving the pulmonary branch of vagus nerve may reduce the incidence of postoperative cough. Therefore, the aim of this study was to investigate whether preserving the pulmonary branch of the vagus nerve could reduce the incidence of postoperative chronic cough in patients with stage I peripheral lung adenocarcinoma. METHODS: A total of 125 patients who underwent single-port thoracoscopic radical resection for lung cancer in the Department of Thoracic Surgery, The First Affiliated Hospital of University of Science and Technology of China from June 2022 to June 2023 were retrospectively selected, and divided into two groups according to whether the vagopulmonary branch was preserved during the operation, namely, the vagopulmonary branch group (n=61) and the traditional group (n=64). The general clinical data, perioperative conditions, lymph node dissection, Mandarin Chinese version of The Leicester Cough Questionnaire (LCQ-MC) scores before and 8 weeks after operation were recorded in the two groups. Both the two groups were divided into tamponade group and non-tamponade group according to whether autologous fat or gelatin sponge was tamponade after lymph node dissection. LCQ-MC scores and postoperative chronic cough of both groups were calculated. RESULTS: The LCQ-MC score of the traditional group was significantly lower than that of the vagopulmonary branch group in physiological, psychological, social and total scores at 8 weeks after surgery, and the difference was statistically significant (P<0.05). There were more cough patients in the traditional group than the vagopulmonary branch group at 8 weeks after surgery, with significant difference (P=0.006). Subgroup analysis was conducted separately for the vagopulmonary branch group and the traditional group. Among the patients in the vagopulmonary branch group and the traditional group, the LCQ-MC scores of the non-tamponade group 8 weeks after surgery were lower than those of the tamponade group (P<0.05). There were more patients with cough in the group 8 weeks after surgery than in the tamponade group (P=0.001, P=0.024). CONCLUSIONS: For patients with stage I peripheral lung adenocarcinoma, the preservation of the pulmonary branch of vagus nerve is safe and effective, which can reduce the incidence of postoperative chronic cough and improve the postoperative quality of life of the patients.

[Establishment of a Predictive Model for Chronic Cough after Pulmonary Resection].

BACKGROUND: Chronic cough after pulmonary resection is one of the most common complications, which seriously affects the quality of life of patients after surgery. Therefore, the aim of this study is to explore the risk factors of chronic cough after pulmonary resection and construct a prediction model. METHODS: The clinical data and postoperative cough of 499 patients who underwent pneumonectomy or pulmonary resection in The First Affiliated Hospital of University of Science and Technology of China from January 2021 to June 2023 were retrospectively analyzed. The patients were randomly divided into training set (n=348) and validation set (n=151) according to the principle of 7:3 randomization. According to whether the patients in the training set had chronic cough after surgery, they were divided into cough group and non-cough group. The Mandarin Chinese version of Leicester cough questionnare (LCQ-MC) was used to assess the severity of cough and its impact on patients' quality of life before and after surgery. The visual analog scale (VAS) and the self-designed numerical rating scale (NRS) were used to evaluate the postoperative chronic cough. Univariate and multivariate Logistic regression analysis were used to analyze the independent risk factors and construct a model. Receiver operator characteristic (ROC) curve was used to evaluate the discrimination of the model, and calibration curve was used to evaluate the consistency of the model. The clinical application value of the model was evaluated by decision curve analysis (DCA). RESULTS: Multivariate Logistic analysis screened out that preoperative forced expiratory volume in the first second/forced vital capacity (FEV1/FVC), surgical procedure, upper mediastinal lymph node dissection, subcarinal lymph node dissection, and postoperative closed thoracic drainage time were independent risk factors for postoperative chronic cough. Based on the results of multivariate analysis, a Nomogram prediction model was constructed. The area under the ROC curve was 0.954 (95%CI: 0.930-0.978), and the cut-off value corresponding to the maximum Youden index was 0.171, with a sensitivity of 94.7% and a specificity of 86.6%. With a Bootstrap sample of 1000 times, the predicted risk of chronic cough after pulmonary resection by the calibration curve was highly consistent with the actual risk. DCA showed that when the preprobability of the prediction model probability was between 0.1 and 0.9, patients showed a positive net benefit. CONCLUSIONS: Chronic cough after pulmonary resection seriously affects the quality of life of patients. The visual presentation form of the Nomogram is helpful to accurately predict chronic cough after pulmonary resection and provide support for clinical decision-making.

Prognostic impact of spread through air spaces in patients with ≤2 cm stage IA lung adenocarcinoma.

Background: In 2015, the World Health Organization (WHO) included spread through air space (STAS) as a new invasive mode of lung cancer. As a new mode of lung cancer dissemination, STAS has a significant and negative impact on patient prognosis. The surgical approach as well as lymph node dissection (LND) for STAS-positive patients is currently unclear. The aim of this study was to investigate the impact of different surgical approaches to STAS and LND on the prognosis of patients with ≤2 cm stage IA lung adenocarcinoma (LUAD). This study also investigated the possible relationship between STAS and the micropapillary histological subtype and its impact on patient prognosis. Methods: A total of 212 patients with LUAD were included in this study from January 2016 to December 2017, and the overall survival (OS) of the patients was compared. The chi-square test and t-test were applied to compare the clinicopathological data of the patients, and the Cox model was used for the multivariate survival analysis. Results: Of the 212 patients, 93 (43.9%) were STAS positive. The univariate analysis showed that the surgical approach, LND type, micropapillary pattern (MP), solid pattern, and STAS were risk factors for OS. The multivariate analysis showed that the surgical approach, MP, and STAS were risk factors for OS. The STAS-positive patients who underwent lobectomy had a better prognosis than those who underwent sublobar resection; however, there was no significant difference between the two surgical procedures in the STAS-negative group. Additionally, the STAS-positive patients who underwent systematic lymph node dissection (SLND) had a better prognosis than those who underwent limited lymph node dissection (LLND); however, there was no significant difference between the two LNDs in the STAS-negative group. Conclusions: STAS plays an important role in patient prognosis and is an independent risk factor for OS of patients with ≤2 cm stage IA LUAD. When STAS is positive, the choice of lobectomy with SLND may result in a better long-term prognosis for patients.

m6A modification of lncRNA PHKA1-AS1 enhances Actinin Alpha 4 stability and promotes non-small cell lung cancer metastasis.

Cancer is a disease with molecular heterogeneity that is closely related to gene mutations and epigenetic changes. The principal histological subtype of lung cancer is non-small cell lung cancer (NSCLC). Long noncoding RNA (lncRNA) is a kind of RNA that is without protein coding function, playing a critical role in the progression of cancer. In this research, the regulatory mechanisms of lncRNA phosphorylase kinase regulatory subunit alpha 1 antisense RNA 1 (PHKA1-AS1) in the progression of NSCLC were explored. The increased level of N6-methyladenosine (m6A) modification in NSCLC caused the high expression of PHKA1-AS1. Subsequently, high-expressed PHKA1-AS1 significantly facilitated the proliferation and metastasis of NSCLC cells, and these effects could be reversed upon the inhibition of PHKA1-AS1 expression, both in vivo and in vitro. Additionally, the target protein of PHKA1-AS1 was actinin alpha 4 (ACTN4), which is known as an oncogene. Herein, PHKA1-AS1 could enhance the protein stability of ACTN4 by inhibiting its ubiquitination degradation process, thus exerting the function of ACTN4 in promoting the progress of NSCLC. In conclusion, this research provided a theoretical basis for further exploring the potential mechanism of NSCLC metastasis and searching novel biomarkers related to the pathogenesis and progression of NSCLC.

The Prognostic Value of the GNRI in Patients with Stomach Cancer Undergoing Surgery.

Malnutrition often induces an adverse prognosis in cancer surgery patients. The elderly nutrition risk index (GNRI) is an example of the objective indicators of nutrition-related risks. We performed a meta-analysis to thoroughly examine the evidence for the GNRI in predicting the outcomes of patients undergoing stomach cancer surgery. Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by 24 October 2022. The clinical outcomes were overall survival (OS), cancer-specific survival (CSS), and post-operative complications. A total of 11 articles with 5593 patients were included in this meta-analysis. The combined forest plot showed that for every unit increase in the preoperative GNRI score in patients with stomach cancer, their postoperative mortality was reduced by 5.6% (HR: 0.944; 95% CI: 0.933−0.956, p < 0.001). The pooled results also demonstrated that a low GNRI was correlated with poor OS (HR: 2.052; 95% CI: 1.726−2.440, p < 0.001) and CSS (HR: 1.684; 95% CI: 1.249−2.270, p = 0.001) in patients who underwent stomach cancer surgery. Postoperative complications were more likely to occur in patients with a low GNRI, as opposed to those with a high GNRI (OR: 1.768; 95% CI: 1.445−2.163, p < 0.001). There was no evidence of significant heterogeneity, and the sensitivity analysis supported the stability and dependability of the above results. the GNRI is a valuable predictor of long-term outcomes and complications in stomach cancer patients undergoing surgery.

[Establishment and Verification of Benign and Malignant Prediction Model of 
Subcentimeter Pulmonary Ground Glass Nodules Based on HRCT].

BACKGROUND: Pre-operative accuracy of subcentimeter ground glass nodules (SGGNs) is a difficult problem in clinical practice, but there are few clinical studies on the benign and malignant prediction model of SGGNs. The aim of this study was to help identify benign and malignant lesions of SGGNs based on the imaging features of high resolution computed tomography (HRCT) and the general clinical data of patients, and to build a risk prediction model. METHODS: This study retrospectively analyzed the clinical data of 483 patients with SGGNs who underwent surgical resection and were confirmed by histology from the First Affiliated Hospital of University of Science and Technology of China from August 2020 to December 2021. The patients were divided into the training set (n=338) and the validation set (n=145) according to 7:3 random assignment. According to the postoperative histology, they were divided into adenocarcinoma group and benign lesion group. The independent risk factors and models were analyzed by univariate analysis and multivariate Logistic regression. The receiver operator characteristic (ROC) curve was constructed to evaluate the model differentiation, and the calibration curve was used to evaluate the model consistency. The clinical application value of the decision curve analysis (DCA) evaluation model was drawn, and the validation set data was substituted for external verification. RESULTS: Multivariate Logistic analysis screened out patients' age, vascular sign, lobular sign, nodule volume and mean-CT value as independent risk factors for SGGNs. Based on the results of multivariate analysis, Nomogram prediction model was constructed, and the area under ROC curve was 0.836 (95%CI: 0.794-0.879). The critical value corresponding to the maximum approximate entry index was 0.483. The sensitivity was 76.6%, and the specificity was 80.1%. The positive predictive value was 86.5%, and the negative predictive value was 68.7%. The benign and malignant risk of SGGNs predicted by the calibration curve was highly consistent with the actual occurrence risk after sampling 1,000 times using Bootstrap method. DCA showed that patients showed a positive net benefit when the predictive probability of the predicted model probability was 0.2 to 0.9. CONCLUSIONS: Based on preoperative medical history and preoperative HRCT examination indicators, the benign and malignant risk prediction model of SGGNs was established to have good predictive efficacy and clinical application value. The visualization of Nomogram can help to screen out high-risk groups of SGGNs, providing support for clinical decision-making.

Altered functional connectivity of the nucleus tractus solitarii in patients with chronic cough after lung surgery: an rs-fMRI study.

BACKGROUND: To explore the altered functional connectivity (FC) of the nucleus tractus solitarii (NTS) in patients with chronic cough after lung surgery using resting-state functional magnetic resonance imaging (rs-fMRI), and the association between abnormal FC and clinical scale scores. METHODS: A total of 22 patients with chronic cough after lung surgery and 22 healthy controls were included. Visual analog scale (VAS), Mandarin Chinese version of the Leicester Cough Questionnaire (LCQ-MC), and Hamilton anxiety rating scale (HAMA) scores were assessed, and rs-fMRI data were collected. The FC analysis was performed using the NTS as the seed point, and FC values with all voxels in the whole brain were calculated. A two-sample t-test was used to compare FC differences between the two groups. The FC values of brain regions with differences were extracted and correlated with clinical scale scores. RESULTS: In comparison to healthy controls, FC values in the NTS and anterior cingulate cortex(ACC) were reduced in patients with chronic cough after lung surgery (GRF correction, p-voxel < 0.005, p-cluster < 0.05) which were positively correlated with LCQ-MC scores (r = 0.534, p = 0.011), but with VAS (r = -0.500, p = 0.018), HAMA (r = -0.713, p < 0.001) scores were negatively correlated. CONCLUSIONS: Reduced FC of the NTS with ACC may be associated with cough hypersensitivity and may contribute to anxiety in patients with chronic cough after lung surgery.

Mechanism of electroacupuncture at acupoints of the lung meridian through PKA/PKC regulation of TRPV1 in chronic cough after lung surgery in guinea pigs.

Background: Acupuncture has achieved good results in the treatment of cough, asthma, chronic obstructive pulmonary disease (COPD) and other lung diseases, but the mechanism associated with acupuncture in the treatment of chronic cough induced by lung surgery is unknown. We investigated whether acupuncture therapy could improve the symptoms of chronic cough after lung surgery through cyclic-AMp dependent protein kinase A (PKA)/cyclic-AMp dependent protein kinase C (PKC) regulation of the transient receptor potential vanilloid-1 (TRPV1) signaling pathway. Methods: The guinea pigs were divided into 5 groups: the Sham operation Group (Sham), the Model Group (Model), the Electroacupuncture + Model Group (EA + M), the H89 + Model Group (H89 + M) and the Go6983 + Model Group (Go6983 + M). The effect of treatment was determined by measuring cough symptoms (number of coughs/cough incubation period) as the outcome criterion. The levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and blood were determined by enzyme-linked immunosorbent assays (ELISA). Lung tissue was stained with hematoxylin and eosin (H&E). The expression of p-PKA, p-PKC and p-TRPV1 proteins was measured by Western blotting. The mRNA levels of TRPV1, Substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinin-1R (NK1R) were measured by real-time polymerase chain reaction (RT-PCR). Results: Acupuncture significantly reduced the cough frequency and prolonged the cough latency of chronic cough in guinea pigs after lung surgery. In addition, acupuncture reduced the damage to lung tissue. The levels of inflammatory cytokines decreased in all treatment groups, the expression levels of p-PKA, p-PKC and p-TRPV1 were significantly inhibited and the mRNA levels of TRPV1, SP, CGRP and NK1R decreased significantly after acupuncture treatment. Conclusions: Acupuncture therapy ameliorated chronic cough in guinea pigs after lung surgery by regulating the TRPV1 signaling pathway via PKA/PKC. Our results showed that acupuncture may be an effective treatment of chronic cough after lung surgery, and also clarified the potential mechanism, which provides a theoretical basis for the clinical treatment of patients with chronic cough after lung surgery.

Preparation, characterization and related in vivo release, safety and toxicity studies of long acting lanreotide microspheres.

The goal of this project was to prepare long-acting lanreotide acetate poly(lactic-co-glycolic acid) (PLGA) microspheres and to analyze the in vivo and in vitro release, safety and toxicology of these preparations. Long-acting lanreotide acetate PLGA microspheres that exhibited a 5-week slow-release period were prepared by a multiple-emulsion solvent evaporation method. Physical characterization, as well as the analysis of the in vivo and in vitro release, safety, acute toxicity and chronic toxicity of the lanreotide microspheres, were conducted in animal models in rats, guinea pigs, rabbits and beagle dogs. The lanreotide acetate PLGA microspheres prepared by multiple-emulsion solvent evaporation had smooth surfaces, uniform particle size and stable lanreotide loading. In vivo and in vitro experiments showed that the lanreotide acetate PLGA microspheres could continuously release lanreotide for 5 weeks. The safety of these long acting lanreotide microspheres was good in the following animal models: active systemic anaphylaxis test in guinea pigs, passive cutaneous anaphylaxis test in rats, hemolytic test in rabbits, local skin irritation test after subcutaneous administration in rabbits and muscle stimulation test in rabbits. Furthermore, no significant acute toxicity or chronic toxicity was observed after administration of lanreotide acetate PLGA microspheres in beagle dogs at dosages up to 22 mg/kg. The lanreotide acetate PLGA microspheres that were prepared in this study exhibited beneficial characteristics in apparent property and structural stability, as well as in release trends in vivo and in vitro.

Sequential pulmonary resections by uniportal video-assisted thoracic surgery for bilateral multiple pulmonary nodules.

Objective: The aim of this study was to evaluate the effect of sequential pulmonary resections by uniportal video-assisted thoracoscopic surgery (VATS) for bilateral multiple pulmonary nodules (BMPNs). Methods: A single-center, prospective, nonrandomized study was performed on patients who underwent one-stage or two-stage operations by uniportal VATS. The clinical, pathological and perioperative data were summarized and analyzed from January 2021 to December 2021. Results: A total of 80 patients were included during the study period. Sequential pulmonary resection by uniportal VATS was underwent in 40 patients. There were no perioperative deaths and serious complications, 2 patients had postoperative pneumonia, 3 patients had transient atrial fibrillation, 1 patient had persistent severe air leakage, 1 patient occurred hemoptysis. The one-stage group had less operative time, surgical blood loss, pleural drainage, chest tube duration and postoperative admission duration(P<0.05). The results of pathological examination of pulmonary nodules revealed adenocarcinoma in situ (n=12), minimally invasive adenocarcinoma (n=24), invasive adenocarcinoma (n=42), squamous carcinoma (n=1),and benign nodules (n=10). The pathological diagnosis included multiple primary lung cancers (30/40, 75%), single primary lung cancer (6/40, 15%). The most advanced pathologic stage of the primary lung cancer was classified as IA (n=19), IB (n=5), II (n=3), and IIIA (n=2). Conclusion: For patients with excellent pulmonary function, sequential pulmonary resection by uniportal VATS is a safe and feasible for BMPNs. Strict control of surgical indications, reasonable preoperative planning, accurate intraoperative operation, and standardized perioperative management can effectively reduce complications and maximize benefits for suitable patients.

The prognostic influence of histological subtypes of micropapillary tumors on patients with lung adenocarcinoma ≤ 2 cm.

Objective: This study aimed to explore the value of micropapillary histological subtypes in predicting the specific surgical specificity and lymph node metastasis prognosis of early lung adenocarcinoma. Methods: A total of 390 patients with lung adenocarcinoma were included who underwent surgery in the Department of Thoracic Surgery of the Affiliated Provincial Hospital of Anhui Medical University from January 2016 to December 2017. The data were analysed with SPSS 26.0 statistical software, and the clinicopathological data of the two groups were compared with the chi-square test. The survival rate was calculated by the Kaplan-Meier method, and the difference in survival rate between groups was analysed by the log-rank test. Multivariate survival analysis was performed using the Cox model. Results: Univariate analysis of the clinicopathological data of the patients showed that the micropapillary histological subtype was significantly associated with the survival rate of patients (p=0.007). The clinicopathological data of the patients were substituted into the Cox model for multivariate analysis, and the results showed that the micropapillary histological subtype was an independent prognostic factor affecting the survival rate of the patients (p=0.009).The average survival time of Group A (micronipple composition > 5%) was 66.7 months; the 1-year, 3-year, and 5-year survival rates were 98.8%, 93.0%, and 80.9%, respectively.The survival of the lobectomy group was better than that of the sublobectomy group and the survival of patients with systematic dissection was better than that of patients with limited lymph node dissection. The average survival time of Group B (micronipple composition ≤ 5%) was 70.5 months; the 1-year, 3-year, and 5-year survival rates were 99.3%, 95.4%, and 90.6%, respectively. There was no difference in the survival rate between the lobectomy group and sublobectomy group, and there was also no difference in survival between systematic lymph node dissection and limited lymph node dissection, The survival rate of Group B was significantly better than that of Group A. Conclusion: The micropapillary histological component is an independent risk factor after surgery in patients with ≤2 cm lung adenocarcinoma. When the proportion of micropapillary components is different, the prognosis of patients is different when different surgical methods and lymph node dissections are performed. Lobectomy and systematic lymph node dissection are recommended for patients with a micropapillary histological composition >5%; sublobar resection and limited lymph node dissection are recommended for patients with a micropapillary histological composition ≤5%.

Relieving the Incompatibility of Network Representation and Classification for Long-Tailed Data Distribution.

In the real-world scenario, data often have a long-tailed distribution and training deep neural networks on such an imbalanced dataset has become a great challenge. The main problem caused by a long-tailed data distribution is that common classes will dominate the training results and achieve a very low accuracy on the rare classes. Recent work focuses on improving the network representation ability to overcome the long-tailed problem, while it always ignores adapting the network classifier to a long-tailed case, which will cause the "incompatibility" problem of network representation and network classifier. In this paper, we use knowledge distillation to solve the long-tailed data distribution problem and fully optimize the network representation and classifier simultaneously. We propose multiexperts knowledge distillation with class-balanced sampling to jointly learn high-quality network representation and classifier. Also, a channel activation-based knowledge distillation method is also proposed to improve the performance further. State-of-the-art performance on several large-scale long-tailed classification datasets shows the superior generalization of our method.

Bruceine D induces lung cancer cell apoptosis and autophagy via the ROS/MAPK signaling pathway in vitro and in vivo.

Worldwide, lung cancer remains a leading cause of cancer mortality. Bruceine D (BD) has been shown to induce pancreatic cancer cell death via several different mechanisms. In this study, we demonstrated that BD inhibited lung cancer cell proliferation. Apoptosis and autophagy were the most important mechanisms involved in BD-induced lung cancer cell death, and complete autophagic flux was observed in A549 and NCI-H292 cells. In addition, BD significantly improved intracellular reactive oxygen species (ROS) levels. BD-mediated cell apoptosis and autophagy were almost inhibited in cells pretreated with N-acetylcysteine (NAC), an ROS scavenger. Furthermore, MAPK signaling pathway activation contributed to BD-induced cell proliferation inhibition and NAC could eliminate p-ERK and p-JNK upregulation. Finally, an in vivo study indicated that BD inhibited the growth of lung cancer xenografts. Overall, BD is a promising candidate for the treatment of lung cancer owing to its multiple mechanisms and low toxicity.

Molecular cloning and characterization of a novel gene encoding zinc finger protein from Medicago sativa L.

A suppression subtraction hybridization (SSH) cDNA library had been constructed to identify differentially expressed genes. Based on the sequence of an expressed sequence tag (EST) homologous to Pisum sativum zinc finger protein mRNA (Accession number: AF160911), the full-length cDNA of 1,676 nucleotides was cloned from alfalfa by rapid amplification of cDNA ends (RACE). It was designated as MsZFN, encoding a protein of 418 amino acids. The amino acid sequence compared by blast revealed high homology with zinc finger protein of other plants. Sequence comparison showed that there were five conserved typical zinc finger motifs, and one sugar transfer protein signature. The calculated molecular weight of the MsZFN protein was 45.8 k Da, and theoretical isoelectric point was 8.13. The MsZFN localized in nucleus. Under normal growth conditions, differential expression of MsZFN exhibited that the expression was the highest in leaf and the lowest in root. MsZFN was quickly and transiently induced by NaCl treatment and reached its maximum at 30 min.

Isolation and characterization of a cDNA encoding a papain-like cysteine protease from alfalfa.

Protein hydrolyzation is activated and involved in response to various stress signals. In the present study, a full-length cDNA, named MsCP1, encoding a papain-like cysteine protease was obtained by degenerated primers and 3'- and 5'-RACE from salt-tolerant alfalfa. The cDNA contained an open reading frame encoding a deduced protein of 350 amino acids with a putative N-terminal signal peptide, NPIR vacuole-sorting signal sequence and potential N-linked glycosylation sites. The deduced sequence showed a high similarity to deduced proteins from pea, tobacco, tomato and ryegrass. Fusion expression analysis in Escherichia coli showed that the putative eukaryotic signal peptide prevented its expression in prokaryotic system. The integration and transcript of the expression elements in transgenic tobacco plants were detected with Southern blot and RT-PCR analysis.

Comparison of automated 4D-MSPECT and visual analysis for evaluating myocardial perfusion in coronary artery disease.

The aim of this study was to assess the reproducibility and diagnostic performance for coronary artery disease (CAD) of an automated software package, 4D-MSPECT, and compare the results with a visual approach. We enrolled 60 patients without previously known CAD, who underwent dual-isotope rest Tl-201/stress Tc-99m sestamibi myocardial perfusion imaging and subsequent coronary angiography within 3 months. The automated summed stress score (A-SSS), summed rest score (A-SRS) and summed difference score (A-SDS) were obtained using a 17-segment five-point scale model with 4D-MSPECT. For intraobserver and interobserver variability assessment, automated scoring was done by a nuclear medicine physician twice and by a nuclear medicine technologist. The visual summed stress score (V-SSS), summed rest score (V-SRS), and summed difference score (V-SDS) were obtained by consensus of two nuclear medicine physicians. The intraobserver and interobserver agreements of automated segmental scores were excellent. The intraobserver and interobserver summed scores also correlated well. Agreements between visual and automated segmental scores were moderate (weighted kappa of 0.55 and 0.50 for stress and rest images, respectively). Correlations between automated and visual summed scores were high, with correlation coefficients of 0.89, 0.85 and 0.82 for SSS, SRS and SDS, respectively (all p < 0.001). The receiver operating characteristic area under the curve for diagnosis of CAD by V-SSS, V-SDS, A-SSS and A-SDS were 0.78 +/- 0.06, 0.87 +/- 0.05, 0.84 +/- 0.05 and 0.90 +/- 0.04, respectively. A-SDS had better diagnostic performance than A-SSS and V-SSS (p = 0.043 and p = 0.032, respectively), whereas there was no statistically significant difference between A-SDS and V-SDS (p = 0.56). Using V-SDS > or = 2 as a diagnostic threshold, the sensitivity, specificity, and accuracy for CAD were 83.7%, 76.5% and 81.7%, respectively. Using A-SDS > or = 3 as a diagnostic threshold, the sensitivity, specificity, and accuracy for CAD were 79.1%, 82.4% and 80.0%, respectively. In conclusion, the reproducibility of automated semiquantitative analysis with 4D-MSPECT was excellent. The diagnostic performance of automated semiquantitative analysis with 4D-MSPECT was comparable with the visual approach.