A G-quadruplex-binding platinum complex induces cancer mitochondrial dysfunction through dual-targeting mitochondrial and nuclear G4 enriched genome.

BACKGROUND: G-quadruplex DNA (G4) is a non-canonical structure forming in guanine-rich regions, which play a vital role in cancer biology and are now being acknowledged in both nuclear and mitochondrial (mt) genome. However, the impact of G4-based targeted therapy on both nuclear and mt genome, affecting mt function and its underlying mechanisms remain largely unexplored. METHODS: The mechanisms of action and therapeutic effects of a G4-binding platinum(II) complex, Pt-ttpy, on mitochondria were conducted through a comprehensive approaches with in vitro and in vivo models, including ICP-MS for platinum measurement, PCR-based genetic analysis, western blotting (WB), confocal microscope for mt morphology study, extracellular flux analyzer, JC1 and Annexin V apoptosis assay, flow cytometry and high content microscope screening with single-cell quantification of both ROS and mt specific ROS, as well as click-chemistry for IF study of mt translation. Decipher Pt-ttpy effects on nuclear-encoded mt related genes expression were undertaken via RNA-seq, Chip-seq and CUT-RUN assays. RESULTS: Pt-ttpy, shows a highest accumulation in the mitochondria of A2780 cancer cells as compared with two other platinum(II) complexes with no/weak G4-binding properties, Pt-tpy and cisplatin. Pt-ttpy induces mtDNA deletion, copy reduction and transcription inhibition, hindering mt protein translation. Functional analysis reveals potent mt dysfunction without reactive oxygen species (ROS) induction. Mechanistic study provided first evidence that most of mt ribosome genes are highly enriched in G4 structures in their promoter regions, notably, Pt-ttpy impairs most nuclear-encoded mt ribosome genes' transcription through dampening the recruiting of transcription initiation and elongation factors of NELFB and TAF1 to their promoter with G4-enriched sequences. In vivo studies show Pt-ttpy's efficient anti-tumor effects, disrupting mt genome function with fewer side effects than cisplatin. CONCLUSION: This study underscores Pt-ttpy as a G4-binding platinum(II) complex, effectively targeting cancer mitochondria through dual action on mt and nuclear G4-enriched genomes without inducing ROS, offering promise for safer and effective platinum-based G4-targeted cancer therapy.

Electronic Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: Long-Term Results of a Multicenter, Randomized, Controlled Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported superior symptom control of electronic patient-reported outcome (ePRO)-based symptom management after lung cancer surgery for up to 1 month postdischarge. Here, we present the long-term results (1-12 months) of this multicenter, randomized trial, where patients were assigned 1:1 to receive postoperative ePRO-based symptom management or usual care daily postsurgery, twice weekly postdischarge until 1 month, and at 3, 6, 9, and 12 months postdischarge. Long-term patient-reported outcomes were assessed with MD Anderson Symptom Inventory-Lung Cancer module. Per-protocol analyses were performed with 55 patients in the ePRO group and 57 in the usual care group. At 12 months postdischarge, the ePRO group reported significantly fewer symptom threshold events (any of the five target symptom scored ≥4; median [IQR], 0 [0-0] v 0 [0-1]; P = .040) than the usual care group. From 1 to 12 months postdischarge, the ePRO group consistently reported significantly lower composite scores for physical interference (estimate, -0.86 [95% CI, -1.32 to -0.39]) and affective interference (estimate, -0.70 [95% CI, -1.14 to -0.26]). Early intensive ePRO-based symptom management after lung cancer surgery reduced symptom burden and improved functional status for up to 1 year postdischarge, supporting its integration into standard care.

Approaches and challenges in identifying, quantifying, and manipulating dynamic mitochondrial genome variations.

Mitochondria, the cellular powerhouses, possess their own unique genetic system, including replication, transcription, and translation. Studying these processes is crucial for comprehending mitochondrial disorders, energy production, and their related diseases. Over the past decades, various approaches have been applied in detecting and quantifying mitochondrial genome variations with also the purpose of manipulation of mitochondria or mitochondrial genome for therapeutics. Understanding the scope and limitations of above strategies is not only fundamental to the understanding of basic biology but also critical for exploring disease-related novel target(s), as well to develop innovative therapies. Here, this review provides an overview of different tools and techniques for accurate mitochondrial genome variations identification, quantification, and discuss novel strategies for the manipulation of mitochondria to develop innovative therapeutic interventions, through combining the insights gained from the study of mitochondrial genetics with ongoing single cell omics combined with advanced single molecular tools.

[Comparison of Quality of Life of the Patients Three Months after Uniportal 
and Multiportal Thoracoscopic Lobectomy].

BACKGROUND: The relationship between quality of life at three months after lung cancer surgery and different surgical approaches is remains unclear. This study aimed to compare the quality of life of patients three months after uniportal and multiportal thoracoscopic lobectomy. METHODS: Data from patients who underwent lung surgery at the Department of Thoracic Surgery, Sichuan Cancer Hospital between April 2021 and October 2021 were collected. The European Organization for Research and Treatment of Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29) were used to collect quality of life data of the patients. Potential confounding factors in the baseline data were included in a multivariate regression model for adjustment, and the quality of life of the two groups three months postoperatively was compared with traditional clinical outcomes. RESULTS: A total of 130 lung cancer patients were included, with 57 males (43.8%) and 73 females (56.2%), and an average age of (57.1±9.5) yr. In the baseline data of the two groups, there was a statistical difference in the number of chest drainage tubes placed (P<0.001). After adjustment with the regression model, at three months postoperatively, there were no significant differences in all symptoms and functional status scores between the two groups (all P>0.05). The multiportal group had longer surgery time (120.0 min vs 85.0 min, P=0.001), postoperative hospital stay (6.0 d vs 4.0 d, P=0.020), and a higher incidence of early ≥ grade 2 complications (39.0% vs 10.1%, P=0.011) compared to the uniportal group. CONCLUSIONS: Patients undergoing uniportal and multiportal thoracoscopic lobectomy have similar quality of life at three months postoperatively. The uniportal group may have certain advantages in terms of traditional clinical outcome indicators such as operation time, postoperative hospital stay, and early postoperative complications.

Relationship between peritoneal solute transport and dialysate inflammatory markers in peritoneal dialysis patients: A cross-sectional study / Relación entre el transporte de soluto peritoneal y los marcadores inflamatorios del diálisis peritoneal en pacientes en diálisis peritoneal: un estudio transversal

Background: The associated factors of peritoneal small solute transport was not fully understood. This research aimed to investigate the connection between dialysate inflammatory markers (e.g. macrophage migration inhibitory factor, MIF) in peritoneal dialysis (PD) effluent and peritoneal solute transport rate (PSTR) properties. Subjects and design: A total of 80 stable PD patients in the First ShaoYang Hospital were enrolled in present study. Overnight PD effluent and serum inflammatory markers including MIF, MCP-1, VEGF, IL-6, TNFα and TGFβ were detected. Pearson correlation analysis and Logistic regression was performed to determine the risk factors for the increased PSTR. Results: A trend toward increased values of MIF, MCP-1 and IL-6 in PD effluent was observed in subjects with high PSTR when compared with those with low PSTR. The Pearson correlation test showed that D/P Cr exhibited positive correlations with dialysis effluent MIF (r=0.32, p=0.01), MCP-1 (r=0.47, p=0.01), IL-6 (r=0.48, p=0.01). Conversely, no significant correlation was found between D/P Cr and TGF-β (r=0.04, p=0.70), TNF-ɑ (r=0.22, p=0.05), VEGF (r=0.02, p=0.86) and serum inflammatory markers. In the unadjusted regression analysis, dialysis effluent MIF (OR 2.41), MCP-1 (OR 1.72), IL-6 (OR 1.55) were associated with high PSTR condition. Multivariate logistic regression analysis showed that the adjusted odds ratios (OR) of dialysis effluent MIF for high PSTR were 2.47 in all subjects (p=0.03). Conclusion: Elevated MIF, MCP-1 and IL-6 levels in PD effluent were associated with increased PSTR. Elevated dialysis effluent MIF levels was an independent risk factor for high PSTR in subjects with PD treatment. (AU)

Antecedentes: Los factores asociados del transporte peritoneal de pequeños solutos no se conocen completamente. Esta investigación tuvo como objetivo investigar la conexión entre los marcadores inflamatorios del dializado (por ejemplo, el factor inhibidor de la migración de macrófagos [MIF]) en el efluente de diálisis peritoneal (DP) y las propiedades de la tasa de transporte de solutos peritoneal (PSTR). Sujetos y diseño: Se incluyó un total de 80 pacientes con DP estable en el primer Hospital de Shaoyang. Se detectaron efluentes de DP nocturnos y marcadores inflamatorios séricos, incluyendo MIF, MCP-1, VEGF, IL-6, TNF -ɑ, TGF -β. Se realizó un análisis de correlación de Pearson y regresión logística para determinar los factores de riesgo para la PSTR aumentada. Resultados: Se observó una tendencia hacia valores incrementados de MIF, MCP-1 e IL-6 en el efluente de DP en sujetos con PSTR alta, en comparación con aquellos con PSTR baja. La prueba de correlación de Pearson mostró que D/Pcr exhibe correlaciones positivas con el MIF del efluente diálisis (r = 0,32, p = 0,01), MCP-1 (r = 0,47, p = 0,01), IL-6 (r = 0,48, p = 0,01). Por el contrario, no se encontró una correlación significativa entre D/Pcr y TGF-β (r = 0,04, p = 0,70), TNF-ɑ (r = 0,22, p = 0,05), VEGF (r = 0,02, p = 0,86) y marcadores séricos de inflamación. En el análisis de regresión no ajustado, el MIF del efluente diálisis (OR 2,41), la MCP-1 (OR 1,72), la IL-6 (OR 1,55) se asociaron con una PSTR elevada. El análisis de regresión logística multivariante mostró que las odds ratios (OR) ajustadas del MIF del efluente diálisis para PSTR alta fueron de 2,47 en todos los sujetos (p = 0,03). Conclusión: Los niveles elevados de MIF, MCP-1 y IL-6 en el efluente de DP se asociaron con un aumento de la PSTR. Los niveles elevados del MIF del efluente diálisis fueron un factor de riesgo independiente para PSTR elevada en sujetos tratados con DP. (AU)

Intrathyroid thymic carcinoma: clinicopathological features and whole exome sequencing analysis.

Intrathyroid thymic carcinoma (ITC) is a rare malignant tumour. We present nine cases of ITC that were analysed by immunohistochemical staining, of which five were analysed using whole exome sequencing (WES). These cases included six women and three men with an age range of 31-66 years. The average postoperative follow-up term was 37.8 months (range, 7-95 months), and all patients survived well except for one case with lung metastasis. Microscopically, ITC showed solid islands of tumour cells separated by fibrous connective tissue containing lymphocytes and other inflammatory cells. Tumour cells strongly expressed Ckpan (AE1/AE3), P63, and CD117. And all cases but one were positive for CD5. The median value of Ki-67 was 32% (range 10-60%). We observed partial positivity of Syn and CgA in only one case. ITC shares morphological and immunohistochemical similarities with thymic squamous cell carcinoma. In situ hybridization of EBER showed negative results. All cases were microsatellite stable, and the tumour mutational burden of the 5 cases was all < 1 mutations/Mb. WES showed higher mutation rates for N4BP1 (2/5), and many genetic alterations were related to the NF-kB signalling pathway, which is crucial for insight into the molecular mechanisms of the occurrence and development of ITC.

Upregulation of long intergenic non-coding RNA LINC00326 inhibits non-small cell lung carcinoma progression by blocking Wnt/ß-catenin pathway through modulating the miR-657/dickkopf WNT signaling pathway inhibitor 2 axis.

BACKGROUND: Long intergenic non-coding RNA 326 (LINC00326) modulates hepatocarcinogenic lipid metabolism. However, the ability of LINC00326 to modulate the highly aggressive non-small cell lung carcinoma (NSCLC) is unknown. Here, LINC00326 in NSCLC was investigated, together with its effects on tumor malignancy and the underlying mechanisms of action. METHODS: LINC00326 levels in tumor tissues and cell lines were measured by Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and RNA fluorescence in situ hybridization (FISH). Proliferation and apoptosis were assessed in cell lines by Cell Counting Kit-8 (CCK-8), EdU staining assays and flow cytometry, respectively, and tumor growth was measured in mouse models. Possible microRNA targets of LINC00326 were predicted by bioinformatics and verified by RNA pull-down and immunoprecipitation and luciferase reporter assays. Western blotting was used to evaluate the expression of Wnt/ß-catenin-associated proteins. RESULTS: LINC00326 was downregulated in tumor tissues and cell lines. Knockdown of LINC00326 stimulated NSCLC cell proliferation and suppressed apoptosis in vitro, as well as enhancing xenograft tumor growth. LINC00326 sponged miR-657, and dickkopf WNT signaling pathway inhibitor 2 (DKK2) was found to be directly targeted by miR-657, with LINC00326 positively regulating its expression through sponging miR-657. The actions of LINC00326 knockdown on proliferation and apoptosis were reversed by stimulation of the miR-657/DKK2 axis. Furthermore, overexpression of miR-657 mitigated DKK2 inhibition on Wnt/ß-catenin signaling. CONCLUSIONS: LINC00326/miR-657/DKK2 axis signaling blocked tumor-associated functions in NSCLC cells through the targeting Wnt/ß-catenin pathway. This suggests that this pathway could be a target for NSCLC treatment.

Longitudinal patient-reported outcomes 1 year after thoracoscopic segmentectomy versus lobectomy for early-stage lung cancer: a multicentre, prospective cohort study protocol.

INTRODUCTION: Segmentectomy and lobectomy are the main surgical procedures for early-stage lung cancer. However, few studies have analysed patient-reported outcomes after segmentectomy versus lobectomy. This study aims to compare patient-reported outcomes-such as symptoms, daily functioning and quality of life-between thoracoscopic segmentectomy and lobectomy for early-stage lung cancer during the 1 year after surgery. METHODS AND ANALYSIS: Overall, 788 newly diagnosed patients with early-stage lung cancer (tumour size ≤2 cm), who are scheduled to undergo thoracoscopic segmentectomy or lobectomy, will be recruited in this multicentre, prospective cohort study. The patients will receive standardised care after surgery. The Perioperative Symptom Assessment for Lung Surgery-a validated lung cancer surgery-specific scale-will be used to assess the symptoms and functions at baseline, at discharge and monthly after discharge for 1 year. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Lung Cancer module 29 will be used to assess the patients' quality of life at the same time points. The primary outcome will be the shortness of breath scores during the first year after thoracoscopic segmentectomy and lobectomy and will be compared using mixed-effects models. The secondary outcomes will include other symptoms, indicators of daily functioning, quality of life scores and traditional clinical outcomes. These will be compared using mixed-effects models and the Student's t-test, non-parametric test or Χ2 test. Propensity score matching will be used to ensure an even distribution of known confounders between the groups. ETHICS AND DISSEMINATION: The Ethics Committee for Medical Research and New Medical Technology of Sichuan Cancer Hospital approved this study (approval number: SCCHEC-02-2022-002). All participants will be instructed to provide informed consent. The manuscript is based on protocol version 3.0. The study results will be presented at medical conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2200060753.

Relationship between peritoneal solute transport and dialysate inflammatory markers in peritoneal dialysis patients: A cross-sectional study.

BACKGROUND: The associated factors of peritoneal small solute transport was not fully understood. This research aimed to investigate the connection between dialysate inflammatory markers (e.g. macrophage migration inhibitory factor, MIF) in peritoneal dialysis (PD) effluent and peritoneal solute transport rate (PSTR) properties. SUBJECTS AND DESIGN: A total of 80 stable PD patients in the First ShaoYang Hospital were enrolled in present study. Overnight PD effluent and serum inflammatory markers including MIF, MCP-1, VEGF, IL-6, TNFα and TGFß were detected. Pearson correlation analysis and Logistic regression was performed to determine the risk factors for the increased PSTR. RESULTS: A trend toward increased values of MIF, MCP-1 and IL-6 in PD effluent was observed in subjects with high PSTR when compared with those with low PSTR. The Pearson correlation test showed that D/P Cr exhibited positive correlations with dialysis effluent MIF (r=0.32, p=0.01), MCP-1 (r=0.47, p=0.01), IL-6 (r=0.48, p=0.01). Conversely, no significant correlation was found between D/P Cr and TGF-ß (r=0.04, p=0.70), TNF-ɑ (r=0.22, p=0.05), VEGF (r=0.02, p=0.86) and serum inflammatory markers. In the unadjusted regression analysis, dialysis effluent MIF (OR 2.41), MCP-1 (OR 1.72), IL-6 (OR 1.55) were associated with high PSTR condition. Multivariate logistic regression analysis showed that the adjusted odds ratios (OR) of dialysis effluent MIF for high PSTR were 2.47 in all subjects (p=0.03). CONCLUSION: Elevated MIF, MCP-1 and IL-6 levels in PD effluent were associated with increased PSTR. Elevated dialysis effluent MIF levels was an independent risk factor for high PSTR in subjects with PD treatment.

miR-657 Targets SRCIN1 via the Slug Pathway to Promote NSCLC Tumor Growth and EMT Induction.

Background: MicroRNA- (miR-) 657 has been shown to regulate immunological and inflammatory activity, and it has also been defined to be dysregulated in both non-small-cell lung cancer (NSCLC) and hepatocellular carcinoma. The mechanistic role whereby miR-657 influences NSCLC progression, however, has yet to be clarified. Methods: miR-657 and SRCIN1 expression levels were assessed via qPCR in the cell lines and tissues of NSCLC. Besides, correlations between the levels of miR-657 and NSCLC patient pathological characteristics were examined, and the Kaplan-Meier approach was employed for the evaluation of the prognostic utility of miR-657 in these patients. Moreover, the Pearson correlation analyses and dual-luciferase reporter assessments were used for detecting interactive relationships between miR-657 and SRCIN1. In addition, CCK-8, EdU, and Transwell assessments were employed for the appraisal of the ability of miR-657/SRCIN1 to regulate NSCLC cell proliferation and invasion. Western blotting was employed for the assessment of the levels of NSCLC cell proteins associated with the epithelial-mesenchymal transition (EMT) that were influenced by miR-657. The nude mice xenograft tumor model is established to observe the effect of miR-657 on NSCLC growth in vivo. Results: NSCLC patient tissues and cell lines exhibited upregulated miR-657 expression that was closely related to tumor differentiation, lymphoid metastasis, and TNM stage. High levels of miR-657 were predictive of a poorer NSCLC patient prognosis, and overexpressing miR-657 resulted in the more rapid growth of NCI-H1650 and A549 cells, with a concomitant increase in their invasion. In addition, miR-657 overexpression raised the levels of Slug, N-cadherin, and Vimentin in these two cell lines while promoting E-cadherin downregulation. Dual-luciferase reporter assays confirmed that miR-657 was capable of binding to the SRCIN1 gene, and SRCIN1 expression levels were negatively associated with those of miR-657, indicating that it acts as a negative regulator of this gene. Knocking down SRCIN1 was capable to reverse the influences of miR-657 inhibitor treatment on NSCLC cell behavior. Finally, in vivo studies showed that miR-657 promoted NSCLC cell growth. Conclusion: The obtained findings illuminate that miR-657 can promote the growth of tumors and the induction of the EMT in NSCLC cells by targeting SRCIN1 expression and modulating Slug pathway activation, highlighting this pathway as a promising therapeutic target in cases suffering from NSCLC.

Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: A Multicenter Randomized Controlled Trial.

PURPOSE: We aimed to evaluate the efficacy and feasibility of patient-reported outcome (PRO)-based symptom management in the early period after lung cancer surgery. METHODS: Before surgery, patients with clinically diagnosed lung cancer were randomly assigned 1:1 to receive postoperative PRO-based symptom management or usual care. All patients reported symptoms on MD Anderson Symptom Inventory-Lung Cancer presurgery, daily postsurgery, and twice a week after discharge for up to 4 weeks via an electronic PRO system. In the intervention group, treating surgeons responded to overthreshold electronic alerts driven by any of the five target symptom scores (score ≥ 4 on a 0-10 scale for pain, fatigue, disturbed sleep, shortness of breath, and coughing). The control group patients received usual care and no alerts were generated. The primary outcome was the number of symptom threshold events (any target symptom with a score of ≥ 4) at discharge. Per-protocol analyses were conducted. RESULTS: Of the 166 participants, 83 were randomly allocated to each group. At discharge, the intervention group reported fewer symptom threshold events than the control group (median [interquartile range], 0 [0-2] v 2 [0-3]; P = .007). At 4 weeks postdischarge, this difference was maintained between the intervention and control groups (median [interquartile range], 0 [0-0] v 0 [0-1]; P = .018). The intervention group had a lower complication rate than the control group (21.5% v 40.6%; P = .019). Surgeons spent a median of 3 minutes managing an alert. CONCLUSION: PRO-based symptom management after lung cancer surgery showed lower symptom burden and fewer complications than usual care for up to 4 weeks postdischarge.

MiR-326 mediates malignant biological behaviors of lung adenocarcinoma by targeting ZEB1.

MiR-326 functions as an antioncogene in the several types of cancer. However, the underling mechanisms through which miRNA-326 regulates the anti-carcinogenesis of lung adenocarcinoma have remained elusive. The aim of this study was to explore the role and regulatory mechanism of miR-326 in cell proliferation, invasion, migration and apoptosis in lung adenocarcinoma. Quantitative real-time PCR (qRT-PCR) was used to detect the expression pattern of miR-326 in human bronchial epithelial cells (HBES-2B), 4 kinds of lung adenocarcinoma cell lines (H23, H1975, H2228, H2085) and 20 lung adenocarcinoma tissues. Then, H23 cells were infected with miR-326 mimics, miR-326 inhibitors and si-ZEB1 to build up-regulated miR-326 cell lines, down-regulated ZEB1(zinc-finger-enhancer binding protein 1)cell lines, simultaneous down-regulated ZEB1 and miR-326 cell lines. Moreover, CCK-8 assay, transwell invasion assay, wound healing assay and flow cytometry assay were employed to examine the effects of miR-326 and ZEB1 on the proliferation, invasion, migration and apoptosis abilities of H23 cells. Western blot was performed to explore the effects of miR-326 and ZEB1 on the expression of invasion and migration related proteins N-cadherin, E-cadherin, MMP7, MMP13, SLUG and apoptotic proteins PARP, BAX. On the mechanism, a dual-luciferase reporter gene was used to measure the target relationship between miR-326 and ZEB1. MiR-326 expression was significantly downregulated in lung adenocarcinoma tissues and cells. Overexpression of miR-326 significantly inhibited the malignant behaviors of H23 cells. Mechanically, luciferase reporter assay showed that ZEB1 was a direct target of miR-326. MiR-326 mimic downregulated the expression of ZEB1. Furthermore, knocking down ZEB1 strongly inhibited the proliferation, invasion and migration of H23 cells but promoted apoptosis. MiR-326 could target ZEB1 to inhibit the proliferation, invasion and migration of lung adenocarcinoma cells and promote apoptosis, which is a potential therapeutic target for lung adenocarcinoma.

[Development Status and Thinking of the "Integrated Diagnosis and Treatment, Full-course Management" Model of Lung Cancer- Based on the Experience of the Lung Cancer MDT Team of Sichuan Cancer Hospital].

With the improvement of medical standards, the pattern of disease diagnosis and treatment has also changed. Lung cancer is the most common malignancy and one of the most complicated diseases to diagnose and treat. Multi-disciplinary treatment (MDT) group has unique advantages in the diagnosis and treatment of tumors, but it has not been widely used in China. Therefore, it is discussed and summarized based on the diagnosis and treatment and management experience of our MDT team. The development status and promotion value of the "integrated diagnosis and treatment, full-course management" model of lung cancer are described.

Temporal change of retinal nerve fiber layer reflectance speckle in normal and hypertensive retinas.

This study investigated temporal change of retinal nerve fiber layer (RNFL) reflectance speckle in retinas with ocular hypertensive (OHT) damage and in control retinas from untreated eyes. Experimental OHT damage to rat retinas was induced by laser photocoagulation of the trabecular meshwork. A series of 660 nm reflectance images was collected from isolated retinas at 10-sec intervals. Areas containing speckled texture were selected on nerve fiber bundles. Correlation coefficients between images with different imaging delays were calculated and plotted as a function of delay. To evaluate the temporal change of speckles, decay of correlation coefficients with time was fitted with an exponential function characterized by a time constant τ. Reflectance per unit thickness (σ) of the areas was also measured and low σ was used as a surrogate of OHT damage. Speckle phenomena occurred in the control RNFL and the RNFL with reduced σ. In the control retinas, τ and σ were nearly constant along bundles but differed significantly among bundles in the same retinas. Among the control retinas, σ was similar, whereas τ varied significantly. In the retinas with OHT damage (low σ) τ could be within, greater or lower than the range in controls. The parameters τ and σ provide independent assessment of the RNFL with OHT damage. Measurements of temporal change of RNFL reflectance speckle may offer a method for detecting functional abnormality of the RNFL.

A clinical research of resecting versus preserving azygos vein, thoracic duct and peripheral tissues in the treatment of esophageal cancer / 中国胸心血管外科临床杂志

@#Objective    To compare the clinical efficacy of modified Ivor-Lewis esophagectomy, which preserves azygos vein, thoracic duct and peripheral tissues, and classic Ivor-Lewis esophagectomy, which resects these tissues, in the treatment of esophageal cancer, so as to evaluate whether it is necessary to resect azygos vein, thoracic duct and peripheral tissues in esophagectomy for esophageal cancer. Methods    Patients scheduled for surgical treatment of thoracic esophageal cancer in Department of Thoracic Surgery of Sichuan Cancer Hospital from June 2011 to June 2013 were randomly assigned to the retention group and the resection group, each including 100 patients. The retention group included 87 males and 13 females with an average age of 60.53±7.72 years. In the resection group, there were 80 males and 20 females with an average age of 60.69±7.69 years. Patients in the two groups were compared for the duration of surgery, intraoperative blood loss, postoperative thoracic drainage volume, postoperative complications, and number of dissected lymph nodes, etc. Postoperative relapse and survival rates at 1, 3 and 5 years postoperatively were also followed up and compared for patients in the two groups. Results    There was no statistical difference between the two groups in general patient characteristics, number of dissected lymph nodes, or postoperative pathological stage, etc. (P>0.05). Compared to the resection group, there were shorter duration of surgery, less intraoperative blood loss, and less thoracic drainage   volume in the first 3 days following surgery in the retention group, with statistical differences (P<0.05). There was no statistical difference between the two groups in type or site of relapse or metastasis (P>0.05). The survival rates at 1, 3, and 5 years postoperatively was 78.7% vs. 81.3%, 39.4% vs. 37.5%, and 23.4% vs. 17.7%, respectively, in the retention group and the resection group, with no statistical difference (P>0.05). Conclusion    Modified Ivor-Lewis esophagectomy preserving azygos vein, thoracic duct and peripheral tissues could reduce surgical trauma, would not increase postoperative relapse or metastasis, and could produce long-term efficacy comparable to that of extended resection.

Circadian clock gene Per2 downregulation in non­small cell lung cancer is associated with tumour progression and metastasis.

Period2 (Per2) is a key circadian clock gene, and its deregulation contributes to tumour development, including breast cancer. However, the biological function and clinicopathological significance of Per2 in non­small cell lung cancer (NSCLC) remain unclear. The present study aimed to explore the role of Per2 and its relative clinical significance in NSCLC. To analyse Per2 expression in NSCLC specimens, reverse transcription­quantitative polymerase chain reaction was performed, and the results indicated that Per2 expression was markedly downregulated in 83.87% (26/31) of NSCLC samples compared with their adjacent matched tissues. Increased Per2 expression was associated with increased differentiation (P<0.01) and reduced lymph node metastasis (P<0.0001). Functional studies identified that enhancing Per2 expression in A549 cells by lentivirus transduction not only significantly suppressed cell growth, migration and invasion (P<0.05) but also inhibited NSCLC growth and metastasis in vivo. Animal studies and histopathological analysis identified that Per2 expression in A549 cells not only markedly increased expression of tumour anti­oncogenes Bax, P53 and P21 but also inhibited expression of pro­oncogenes vascular endothelial growth factor, CD44 and c­Myc. These results indicate that the loss of Per2 is one of the factors underlying tumourigenesis in NSCLC, and it may function as a novel molecular target for NSCLC.

Moderate fabrication and characterization of the microcrystalline Sr2CuO3 glass films with effective nonlinearities.

Since nonlinear optical materials used in the ultrafast all-optical switching is an important part for the modern optical technology, cuprates have been widely investigated for their specific Cu-O chain structure and intriguing optical properties. We present a new preparation method of microcrystalline Sr2CuO3 glass films on glass substrates combining spin-coating and co-sintering techniques. Then, the as-prepared samples were polished for different times to obtain microcrystalline Sr2CuO3 glass films with varying thickness. The influence of polishing time on the structure, the valence state and the nonlinear optical response were discussed, respectively. The purity of the Sr2CuO3 phase, surface morphology and the chemical composites of these synthesized glass films were given with scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray powder diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). Importantly, optical absorption spectroscopy and Z-scan technique were used to measure linear absorption and third-order optical nonlinearity of the films. The experiments showed that third-order nonlinear susceptibility of the 140 min polished film sample with a thickness of 18 µm was up to 1.23 × 10-12 esu, indicating its potential application in the nonlinear field.

Response of the Retinal Nerve Fiber Layer Reflectance and Thickness to Optic Nerve Crush.

Purpose: To study the effects of acute optic nerve damage on the reflectance of the retinal nerve fiber layer (RNFL) and to compare the time courses of changes of RNFL reflectance and thickness. Methods: A rat model of optic nerve crush (ONC) was compared with previously studied normal retinas. The reflectance and thickness of the RNFL were studied at 1 to 5 weeks after ONC. Reflectance spectra from 400 to 830 nm were measured for eyes with ONC, their contralateral untreated eyes, and eyes with sham surgery. Directional reflectance was studied by varying the angle of light incidence. RNFL thickness was measured by confocal microscopy. Results: After ONC, the RNFL reflectance remained directional. At 1 week, RNFL reflectance decreased significantly at all wavelengths (P < 0.001), whereas there was no significant change in RNFL thickness (P = 0.739). At 2 weeks, both RNFL reflectance and thickness decreased significantly, and by 5 weeks they declined to approximately 40% and 30%, respectively, of the normal values. Although RNFL reflectance decreased at all wavelengths, there was a greater reduction at short wavelengths. Spectral shape at long wavelengths was similar to the normal. Some of these changes were also found in the contralateral untreated eyes, but none of these changes were found in eyes with sham surgery. Conclusions: Decrease of RNFL reflectance after ONC occurs prior to thinning of the RNFL and the decrease is more prominent at short wavelengths. Direct measurement of RNFL reflectance, especially at short wavelengths, may provide early detection of axonal damage.

CHEK2 SNPs predict better prognosis in HBV-related hepatocellular carcinoma patients.

OBJECTIVE: Checkpoint kinase 2 gene (CHEK2) is an important mediator of the DNA damage response pathway. Single nucleotide polymorphisms (SNPs) have been shown to influence the developing risk and clinical characteristics in various types of human malignancies. The values of CHEK2 SNPs in HBV-related hepatocellular carcinoma patients (HCC) were unknown and discussed here. METHODS: The expression and prognostic prediction role of CHEK2 were searched and analyzed in HBV-related HCC patients by GEO database. SNPs in CHEK2 were genotyped by SNP selection tools, and further assessed their associations with clinical outcomes of 339 HBV-related HCC patients. RESULTS: Patients with a higher CHEK2 gene expression predicted a worse relapse free survival (RFS). Moreover, those with a variant alleles CC/TT of SNPs rs1547014 and rs738722 had a significantly better prognosis when compared to the patients with CT genotype (P<0.015 for rs1547014, P=0.001 for rs738722), and CC/TT genotype combined with AFP≤400 ng/ml also predicted the best prognosis in HBV-related HCC patients. In stratified analysis, the protective effect of rs1547014 and rs738722 CC/TT genotype was more evident in patients with adverse strata, comparing the patients with favorable strata. CONCLUSION: CHEK2 SNPs rs1547014 and rs738722 probably be potential prognostic bio-markers in HBV-related HCC patients.