4-hydroxysesamin protects rat with right ventricular failure due to pulmonary hypertension by inhibiting JNK/p38 MAPK signaling.

The specific mechanism of 4-hydroxysesamin (4-HS), a modification of Sesamin, on right ventricular failure due to pulmonary hypertension (PH) is ominous. By creating a rat model of PH in vivo and a model of pulmonary artery smooth muscle cell (PASMC) hypoxia and inflammation in vitro, the current work aimed to investigate in depth the molecular mechanism of the protective effect of 4-HS. In an in vitro model of hypoxia PASMC, changes in cell proliferation and inflammatory factors were detected after treatment with 4-HS, followed by changes in the JNK/p38 MAPK signaling pathway as detected by Western blot signaling pathway. The findings demonstrated that 4-HS was able to minimize PASMC cell death, block the JNK/p38 MAPK signaling pathway, and resist the promoting effect of hypoxia on PASMC cell proliferation. Following that, we found that 4-HS could both mitigate the right ventricular damage brought on by MCT and had a protective impact on rats Monocrotaline (MCT)-induced PH in in vivo investigations. The key finding of this study is that 4-HS may protect against PH by inhibiting the JNK/p38 MAPK signaling pathway.

p16 and p53 can Serve as Prognostic Markers for Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: The present study aimed to explore the expression and clinical significance of human papilloma virus-related pathogenic factors (p16, cyclin D1, p53) in patients with head and neck squamous cell carcinoma (HNSCC) and construct a predictive model. METHODS: The Cancer Genome Atlas was used to obtain clinical data for 112 patients with HNSCC. Expression of p16, p53, and cyclin D1 was quantified. We used the survival package of the R program to set the cut-off value. Values above the cut-off were considered positive, while values below the cut-off were negative. Kaplan-Meier analysis and univariate and multivariate Cox regression analyses were performed to investigate prognostic clinicopathological indicators and the expression of p16, p53, and cyclin D1. A predictive model was constructed based on the results of multifactor Cox regression analysis, and the accuracy of the predictive model was verified through final calibration analysis. Follow-up of patients with HNSCC at the Affiliated Hospital of Binzhou Medical University was conducted from 2015 to 2017, and reliability of the predictive model was validated based on follow-up data and molecular expression levels. RESULTS: According to the results, expression of p16 and p53 was significantly associated with prognosis (P < .05). The predictive model constructed based on the expression levels of p16 and p53 was useful for evaluating the prognosis of patients with HNSCC. The predictive model was validated using follow-up data obtained from the hospital, and the trend of the follow-up results was consistent with the predictive model. CONCLUSION: p16 and p53 can be used as key indicators to predict the prognosis of HNSCC patients and as critical immunohistochemical indicators in clinical practice. The survival model constructed based on p16 and p53 expression levels reliably predicts patient prognosis.

The effects of intrinsic water-use efficiency and climate on wood anatomy.

Climate warming may induce growth decline in warm-temperate areas subjected to seasonal soil moisture deficit, whereas increasing atmospheric CO2 concentration (Ca) is expected to enhance tree growth. An accurate understanding of tree growth and physiological processes responding to climate warming and increasing Ca is critical. Here, we analyzed tree-ring stable carbon isotope and wood anatomical traits of Pinus tabuliformis from Qinling Mountains in China to understand how lumen diameter (LD) determining potential hydraulic conductivity and cell-wall thickness (CWT) determining carbon storage responded to climate and Ca. The effects of climate and Ca on intrinsic water-use efficiency (iWUE) were isolated, and iWUE values due to only-climate (iWUEClim) and only-CO2 effects (iWUECO2) were obtained. During a low-iWUE period, the influences of climate on earlywood (EW) LD and latewood (LW) CWT prevailed. During a high-iWUE period, CO2 fertilization promoted cell enlargement and carbon storage but this was counteracted by a negative influence of climate warming. The limiting direct effects of iWUEClim and indirect effects of climate on EW LD were greater than on LW CWT. P. tabuliformis in temperate forests will face a decline of growth and carbon fixation, but will produce embolism-resistant tracheids with narrow lumen responding to future hotter droughts.

Effects of losartan in patients with NAFLD: A meta-analysis of randomized controlled trial.

Losartan has become a hot spot in the treatment of non-alcoholic fatty liver disease (NAFLD) among angiotensin receptor blocker drugs. We sought to conduct a systematic examination and meta-analysis to examine the effects of losartan on patients with NAFLD. We searched for potentially randomized controlled trials in PubMed, Embase, China National Knowledge Infrastructure, Wanfang, and the Cochrane database up to October 09, 2022. We used the Cochrane risk of bias tool to evaluate the study quality. Analysis of subgroups, sensitivity analysis, and publishing bias were explored. The quality of the included studies was moderate to high. Six trials involving 408 patients were included. The meta-analysis demonstrated that aspartate transaminase was significantly affected by losartan therapy (mean difference [MD] = -5.34, 95% confidence interval [CI] [-6.54, -4.13], Z = 8.70, P < 0.01). The meta-analysis subgroup showed that losartan 50 mg once daily could lower the level of alanine aminotransferase (MD = -18.92, 95% CI [-21.18, -16.66], Z = 16.41, P < 0.01). There was no statistically significant difference in serum total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein.

Associations of Clinical and Molecular Characteristics with the Response to Immune Checkpoint Blockade in Advanced Gastric Cancers.

Purpose: Immunotherapy provides a new treatment option for advanced gastric cancer (AGC). This study aims to explore the response markers of immunotherapy in AGCs. Methods: Next-generation sequencing was performed on 44 AGC patients who received immune checkpoint inhibitors and the associations between their outcomes after combination immunotherapy, and the clinicopathological/molecular characteristics were analyzed. Results: The current study cohort had a median progression-free survival (PFS) of 5.9 months, an overall survival (OS) of 12.1 months, and an objective response rate (ORR) of 36.4%. Through multivariable analysis of the clinical characteristics, primary tumor resection (HR = 2.66, 95% CI: 1.06-6.70, p=0.037) and increased proportion of lymphocytes after combination immunotherapy (HR = 0.40, 95% CI: 0.16-0.99, p=0.048) were revealed as independent predictors for patient outcomes. All the 18 patients who underwent genetic profiling were microsatellite-stable with a median TMB of four mutations per Mb. ATM alterations, PI3K pathway mutations, increased TMB, and positive PD-L1 expression were associated with the increased trend of PFS and ORR. According to the combination of baseline lymphocyte count, ATM mutation, TMB status, and PD-L1 expression, patients were stratified into higher- and lower-risk groups, with the lower-risk group showing improved PFS (HR = 4.7e-10, 95% CI: 0-inf, p=0.02) and ORR (75% vs. 0%, p=0.007). Conclusion: Several highly relevant potential biomarkers predictive of immunotherapy response in AGC patients have been identified in this research.

[Measurement and research status of stable hydrogen isotopes in tree-ring lignin methoxyl groups]. / æ ‘è½®æœ¨è´¨ç´ ç”²æ°§åŸºç¨³å®šæ°¢åŒä½ç´ æ¯”çŽ‡æµ‹å®šæ–¹æ³•ç ”ç©¶è¿›å±•.

The primary hydrogen (H) source for all organic compounds in the biosphere is from water, and then participates in biogeochemical cycles through photosynthesis and plant physiological metabolism. As a new proxy of paleoclimate and paleoenvironment, stable hydrogen isotope ratios in wood lignin methoxyl groups (δ2HLM) show great advantages in the studies of paleoclimatic change and have been used to reconstruct precipitation stable hydrogen isotope ratios and paleoclimate signals in many regions. Based on the lignin application mechanism and analysis method of δ2HLM, we evaluated the stability and effectiveness of δ2HLM-measurement method from lignin content and lignin monomer composition, and expounded the tree lignin methoxyl groups' stable isotope proxies of current research outcomes. In the middle latitudes, the tree-ring δ2HLM had great potential in recording temperature signals and precipitation stable hydrogen isotope ratios. However, the study of tree-ring δ2HLM was still in its infancy as evidenced by following reasons: 1) The study area was limited to the middle latitude of the northern hemisphere, and the study subjects were limited to conifer species; 2) To compensate for the limitation of hydrogen isotopic records of nitrocellulose, high resolution tree-ring δ2HLM would be studied; 3) The potential of tree-ring δ2HLM utilization in plant physiology and forest ecology remained to be exploited.

Association of dyslipidaemia with osteoporosis in postmenopausal women.

OBJECTIVE: To assess the association of dyslipidaemia with osteoporosis in postmenopausal women. METHODS: Data from 160 postmenopausal women with newly diagnosed osteoporosis (osteoporosis group) and 156 healthy controls (control group) were retrospectively reviewed from 2016 to 2020. The primary outcomes were laboratory values assessed by a multivariate binary logistic regression model. RESULTS: Factors that greatly increased the risk of being in the osteoporosis group included high low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) levels. The osteoporosis group had lower HDL and higher LDL levels than the control group. A multivariate binary logistic regression model showed that lower HDL and higher LDL levels were the only variables that were significantly associated with osteoporosis (odds ratio 1.86, 95% confidence interval: 3.66-4.25 and odds ratio 1.47, 95% confidence interval: 1.25-2.74, respectively). CONCLUSION: Low HDL and high LDL levels may be associated with the occurrence of osteoporosis in postmenopausal women.

Integrative clinical and molecular analysis of advanced biliary tract cancers on immune checkpoint blockade reveals potential markers of response.

BACKGROUND: While there have been encouraging preliminary clinical results for immune checkpoint inhibitors (ICIs) in BTCs, it remains a challenge to identify the subset of patients who may benefit. In this study, we evaluated the efficacy of ICI treatment in patients with advanced BTCs, and explored potential biomarkers that are predictive of response. METHODS: The study enrolled 26 patients with advanced microsatellite stable BTCs (15 with gallbladder cancers [GCs] and 11 with intrahepatic cholangiocarcinoma [ICCs]) who received ICI treatment. Targeted next-generation sequencing (NGS) was performed on tumor tissue samples collected from 17 patients. Clinical and genomic characteristics were assessed for the correlation with clinical outcome. RESULTS: Analysis of the baseline clinical characteristics showed that performance score (PS) of 0 was associated with a better prognosis than PS of 1 (HR = 1.08 × 109 ; 95% CI, 0∼Inf; P = .002). No significant correlations were found between clinical outcome and inflammation-related indicators. NGS profiling of the available tumor tissues, revealed largely non-overlapping somatic alterations between GCs and ICCs. Mutations in LRP1B (HR = 0.26; 95% CI, 0.06-1.21; P = .067), ERBB2 (HR = 0.15; 95% CI, 0.02-1.19; P = .04), or PKHD1 (HR < 0.01; 95% CI, 0-Inf; P = .04) showed strong association with increased progression-free survival (PFS) benefit. Subsequent analysis showed that alterations in the RTK-RAS pathway were associated with improved outcomes (HR = 0.12; 95% CI, 0.02-0.63; P = .003). Tumor mutation burden (TMB) was higher in patients with GC than those with ICC, and was associated with LRP1B mutations (P = .032). We found that patients with 19q amplification (19q Amp) and 9p deletion (9p Del) had poor PFS outcome (19q Amp, HR = 15.4; 95% CI, 2.7-88.5; P < .001; 9p Del; HR = 4.88 × 109 ; 95% CI, 0-Inf; P < .001), while those with chromosomal instability derived PFS benefit (HR = 0.24; 95% CI, 0.05-1.17; P = .057). CONCLUSION: Our study identified several potential clinical and genomic features that may serve as biomarkers of clinical response to ICIs in advanced BTCs patients. A larger sample size is required for further verification.

BCCIPß facilitates p53 ubiquitination via binding with E6 protein in high-risk HPV positive head and neck squamous cell carcinoma.

BRCA2 And CDKN1A Interacting Protein (BCCIP) is initially identified as a tumor suppressor. Some recent studies confirmed its p53 binding capability. In this study, we explored the regulatory effect of BCCIPß on p53 stability in HPV-positive and HPV-negative HNSCC cells. RNA-seq data from TCGA-HNSC were extracted for transcript isoform analysis in HPV-positive and HPV-negative tumors. HPV16-positive UM-SCC-47 (SCC47) and UM-SCC-104 (SCC104) and HPV-negative SCC-9 (SCC9) and UM-SCC-1 (SCC1) cell lines were used as in vitro cell models. Results showed that BCCIPß was the dominant transcript in both HPV-positive and HPV-negative HNSCC cases. Knockdown of BCCIPß decreased p53 protein concentration in the two HPV-negative cell lines but increased p53 concentration in the two HPV-positive cell lines. BCCIPß inhibition increased proliferation and G1/S transition of SCC9 and SCC1 cells. In comparison, BCCIPß inhibition slowed proliferation and increased G1 arrest of SCC104 and SCC47 cells. BCCIPß inhibition prolonged the half-life of p53 protein and reduced p53 ubiquitination in the two HPV16-positive cell lines. Co-IP assay confirmed interactions among BCCIPß, HPV E6, and p53 in both SCC104 and SCC47 cells. In comparison, only the interaction between BCCIPα and p53 was confirmed in these two cell lines. Either E6 or BCCIPß inhibition reduced p53 ubiquitination and increased p53 concentration. However, inhibiting E6 and BCCIPß at the same did not generate synergistic effects. On the contrary, p53 ubiquitination level was even higher in the combination group, with lower p53 concentration compared to the shE6 group. BCCIPß overexpression in SCC47 cells with HPV E6 depletion significantly reduced p53 ubiquitination. In conclusion, this study found a novel interaction between HPV E6 and BCCIPß in HPV16-positive HNSCC cells. The presence of HPV E6 turned BCCIPß from a p53 stabilizer to a ubiquitination facilitator. This mechanism helps explain why BCCIPß acted as a tumor suppressor in HPV-negative HNSCC but exerted oncogenic function in HPV16-positive HNSCC.

The CT appearance pattern of radiation-induced lung injury and tumor recurrence after stereotactic body radiation therapy in early stage non-small cell lung cancer.

BACKGROUND: Radiographic changes after stereotactic body radiation therapy (SBRT) have not been well studied. The purpose of this study was to investigate the computed tomography (CT) appearance pattern of radiation-induced lung injury (RILI) and recurrence after SBRT in patients with early stage non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed clinical data of inoperable early stage NSCLC patients undergoing SBRT treatment from February 2012 to June 2018. All patients had undergone serial CT scanning before SBRT and after completion of SBRT. An experienced radiation oncologist and radiologist reviewed all CT images, and identified the RILI and CT high-risk features (HRFs). RESULTS: A total of 60 patients were enrolled in this study; 55 patients had RILI (91.67%) and 7 patients had local failure. In the early CT findings of observers 1 and 2, there were diffuse ground glass opacities (GGOs) in 3 and 4 patients, diffuse consolidation in 10 and 12 patients, patchy consolidation in 22 and 15 patients, patchy GGOs in 19 and 24 patients, and no changes in 5 and 4 patients, respectively (kappa =0.706). In the late CT findings of observer 1 and 2, there were modified conventional patterns in 37 and 37 patients, mass-like patterns in 10 and 9 patients, scar-like patterns in 7 and 8 patients, and no changes in 5 and 5 patients, respectively (kappa =0.726). In the results of the CT-based HRFs of disease local failure, there were ≥1 HRFs in 7 patients, ≥2 HRFs in 7 patients, ≥3 HRFs in 6 patients, ≥4 HRFs in 5 patients, and ≥5 HRFs in 3 patients, respectively. Patients with only 1 HRF showed high sensitivity (100%) and low specificity (52.80%), with the specificity increasing and the sensitivity decreasing as the number of HRFs increased. CONCLUSIONS: The agreement of the CT appearance on RILI between 2 observers was good. Regular follow-up and attention to HRFs are vital for better identifying RILI and local disease failure.

Temperature signal recorded in δ2H and δ13C values of wood lignin methoxyl groups from a permafrost forest in northeastern China.

Stable isotopes in wood lignin methoxyl groups (δ2HLM and δ13CLM values) have been suggested as valuable complementary paleoclimate proxies. In permafrost forests, tree growth is influenced by multiple factors, however temperature appears to have the strongest impact on tree growth and, therefore, on carbon cycling. To test whether δ2HLM and δ13CLM values of trees from permafrost regions might record climate parameters, two dominant tree species (Larix gmelinii, larch, and Pinus sylvestris var. mongolica, pine) collected from a permafrost forest in China's Greater Hinggan Mountains, were investigated. The two tree species larch and pine covered time spans of 1940 to 2013 and 1870 to 2013, respectively. Results showed significant correlations of pine and larch δ2HLM values and larch δ13CLM values with temperatures and in particular with the mean temperature of the growing season from April to August. However, only weak correlations of δ2HLM and δ13CLM values with moisture conditions, such as precipitation amount and relative humidity were observed. In addition, species specificity in the climate response was most obvious for δ13CLM values. Compared to a temperature reconstruction based on tree ring width, pine δ2HLM-based reconstruction showed strongest spatial correlations with regional temperature. Therefore, δ2HLM values might be a promising proxy to reconstruct growing-season temperatures in permafrost regions.

SEMA3A Exon 9 Expression Is a Potential Prognostic Marker of Unfavorable Recurrence-Free Survival in Patients with Tongue Squamous Cell Carcinoma.

This study tried to assess the prognostic value of semaphorin (SEMA) family genes in patients with tongue squamous cell carcinoma (TSCC) and the potential epigenetic alterations of the genes. The part of third-level TSCC data in The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma (TCGA-HNSC) was extracted using the UCSC Xena browser for analysis. Among 20 SEMA genes examined, 7 were markedly upregulated, while 8 were substantially decreased in TSCC tissues compared with adjacent normal tissues. SEMA3A was the only gene with independent prognostic value in terms of recurrence-free survival (RFS) in multivariate analysis (hazard ratio [HR]: 1.697, 95% CI: 1.228-2.345, p = 0.001). Among the individual exons of SEMA3A, the exon 9 had a better prognostic value in terms of recurrence than total SEMA3A expression and its expression also independently predicted shorter RFS (HR: 2.193, 95% CI: 1.463-3.290, p < 0.001). The methylation levels of two CpG sites (cg06144675 and cg13988052) were moderately correlated with SEMA3A expression. Interestingly, cg06144675, which locates at the promoter region, showed a negative correlation with SEMA3A expression, whereas cg13988052, which is in the intron of SEMA3A gene body showed a positive correlation with SEMA3A expression. In conclusion, SEMA3A expression is aberrantly upregulated in TSCC tissues. Its exon 9 expression is a potentially valuable prognostic marker of unfavorable RFS in TSCC patients. Both promoter hypomethylation and gene body hypermethylation might contribute to the dysregulation.

Stereotactic body radiotherapy for early stage non-small cell lung cancer in patients with subclinical interstitial lung disease.

BACKGROUND: For lung cancer patients with subclinical (untreated and asymptomatic) interstitial lung disease (ILD), there is a lack of relatively safe and effective treatment. Stereotactic body radiation therapy (SBRT) can achieve a high level of tumor control with low toxicity in early-stage non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy and toxicity of early stage NSCLC patients with subclinical ILD receiving SBRT. METHODS: A total of 109 early stage NSCLC patients receiving SBRT treatment between December 2011 and August 2016 were reviewed in our institutions; patients with clinical ILD were excluded. The median dose of SBRT was 50 Gy in 5 fractions. The median biologically effective dose (BED; α/ß=10) was 100 Gy (range, 72-119 Gy). An experienced radiation oncologist and an experienced radiologist reviewed the presence of subclinical ILD in the CT findings before SBRT. The relationships among the efficacy, radiation-induced lung injury (RILI) and subclinical ILD were explored. RESULTS: In all, 38 (34.9%) of 109 patients were recognized with subclinical ILD before SBRT, 48 (44.0%) of 109 patients were recognized with grade 2-5 RILI after SBRT, and 18 (47.4%) of 38 patients with subclinical ILD were observed with grade 2-5 RILI. Subclinical ILD was not a significant factor of grade 2-5 RILI (P=0.608); however, 3 patients had extensive RILI, and they all suffered from subclinical ILD. Dosimetric factor of the lungs, such as mean lung dose (MLD) was significantly related with Grade 2-5 RILI in patients with subclinical ILD (P=0.042). The progression-free survival (PFS) rates at 3 years in the subclinical ILD patients and those without ILD were 61.6% and 66.8%, respectively (P=0.266). CONCLUSIONS: Subclinical ILD was not a significant factor for RILI or PFS in early stage NSCLC patients receiving SBRT; however, patients with subclinical ILD receiving SBRT may experience uncommon extensive RILI.

[Effect of concentrated growth factor on the biological properties of MC3T3-E1 osteoblasts].

PURPOSE: To observe the effect of concentrated growth factor(CGF) on the biological properties of osteoblasts. METHODS: MC3T3-E1 cells were cultured in CGF environment and a blank control group was established. The adhesion of osteoblasts to CGF surface was observed by scanning electron microscopy. Cell proliferation and alkaline phosphatase(ALP) activity were detected at 1, 4 and 7 d by Cell Counting Kit-8 (CCK-8) and Alkaline Phosphatase Assay Kit. The expression of mineralized nodules and osteogenesis-related gene Runx2 was observed by alizarin red staining. CGF extract was cultured for 24 h. Peptide staining was used to observe morphological changes in the cytoskeleton. SPSS 21.0 software package was used for statistical analysis. RESULTS: CCK-8 showed cells incubated for 1, 4 and 7 d in the experimental group had a stronger proliferation ability compared with the control group, and the difference was statistically significant (P<0.05). ALP activity test showed that there was no significant difference between the experimental group and the control group (P>0.05) at 1 d; but after 4 days of culture, cell in the experimental group had an increased ALP activity compared with the control group, and the difference was statistically significant(P<0.05). The results of alizarin red staining showed that the number of calcified nodules in the CGF group increased and the area was larger. In the phalloidin staining and DAPI staining, the number of cells in the CGF group increased, the cell spreading surface increased, and the actin shape was clearer. CGF significantly promoted Runx2 mRNA expression(P<0.05). CONCLUSIONS: High concentration of CGF can promote the proliferation and differentiation of MC3T3-E1 cells and the expression level of related osteogenic gene Runx2.

Perineural and lymphovascular invasion predicts for poor prognosis in locally advanced rectal cancer after neoadjuvant chemoradiotherapy and surgery.

Background: Perineural invasion (PNI) and lymphovascular invasion (LVI) are associated with poor prognosis in colorectal cancer, but their clinical significance is still controversial for patients with locally advanced rectal cancer (LARC) who had received neoadjuvant chemoradiotherapy (nCRT) and surgical resection. The aim of this study was to confirm the correlation between PNI and/or LVI and clinical prognosis and to further confirm whether PNI and/or LVI can be used as potential prognostic indicators of adjuvant chemotherapy after nCRT and surgery in LARC. Methods: From February 2002 to December 2012, a total of 181 patients with LARC who had received nCRT and surgical resection were retrospectively reviewed. Overall survival (OS) and disease-free survival (DFS) were determined by the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression model. Results: The median follow-up time was 48 months (range, 3 to 162 months). All the PNI-positive and/or LVI-positive patients showed adverse DFS and OS (P<0.001). In multivariate analysis, PNI and LVI were independent prognostic factors for DFS. PNI, rather than LVI, was also an independent prognostic factor for OS. In a subgroup analysis, PNI-positive, rather than LVI-positive, may benefit from adjuvant chemotherapy. Conclusion: For patients with LARC undergoing nCRT and surgery, PNI-positive and/or LVI positive were associated with poorer DFS and OS. And PNI-positive, rather than LVI-positive, may benefit from adjuvant chemotherapy.

Warming and CO2 enrichment modified the ecophysiological responses of Dahurian larch and Mongolia pine during the past century in the permafrost of northeastern China.

Tree-ring δ13C and δ18O of dominant Dahurian larch and Mongolia pine in the permafrost region of the northern Great Higgnan Mountains, China were used to elucidate species-specific ecophysiological responses to warming temperatures and increasing CO2 over the past century. Larch and pine stable carbon discrimination (Δ13C) 13C and δ18O in tree rings both showed synchronous changes during the investigated period (1901-2010), but with species-specific isotopic responses to atmospheric enriched CO2 and warming. Tree-ring Δ13C and δ18O were controlled by both maximum temperature and moisture conditions (precipitation, relative humidity and vapor pressure deficit), but with different growth periods (Δ13C in June-July and δ18O in July-August, respectively). In addition, stable isotopes of larch showed relatively greater sensitivity to moisture deficits than pine. Climatic conditions from 1920 to 1960 strongly and coherently regulated tree-ring Δ13C and δ18O through stomatal conductance. However, climatic-sensitivities of tree-ring Δ13C and δ18O recently diverged, implying substantial adjustments of stomatal conductance, photosynthetic rate and altered water sources over recent decades, which reveal the varied impacts of each factor on tree-ring Δ13C and δ18O over time. Based on expected changes in leaf gas-exchange, we isolated the impacts of atmospheric CO2 and climate change on intrinsic water-use efficiency (iWUE) over the past century. Higher intracellular CO2 in pine than larch from 1960 onwards suggests this species may be more resilient to severe droughts in the future. Our data also illustrated no weakening of the iWUE response to increasing CO2 in trees from this permafrost region. The overall pattern of CO2 enrichment and climate impacts on iWUE of pine and larch were similar, but warming increased iWUE of larch to a greater extent than that of pine over recent two decades. Taken together, our findings highlight the importance of considering how leaf gas-exchange responses to atmospheric CO2 concentration influence species-specific responses to climate and the alteration of the hydrological environment in forests growing in regions historically dominated by permafrost that will be changing rapidly in response to future warming and increased CO2.

Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy.

BACKGROUND Increasing evidence suggests that cancer-associated inflammation is associated with poorer outcomes. The neutrophil-to-lymphocyte ratio (NLR), considered as a systemic inflammation marker, is thought to predict prognoses in colorectal cancer. In this study, we explored the association between the NLR and prognoses following neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). MATERIAL AND METHODS From February 2002 to December 2012, a group of 202 patients diagnosed with LARC and receiving neoadjuvant CRT followed by radical surgery was included in our retrospective study. The associations between the pre-CRT NLR and clinicopathological characteristics, as well as the predictive value of pre-CRT NLR against survival outcomes, were analyzed. RESULTS The average NLR was 2.7±1.5 (median 2.4, range 0.6-12.8). There were 63 (31.2%) patients with NLR ≥3.0, and 139 (68.8%) patients with NLR <3.0. Correlation analyses showed that no clinicopathological characteristics except age were associated with NLR. We did not find an association between NLR and survival outcomes. In multivariate Cox model analyses, the R1/R2 resection, lymph node ratio ≥0.1, and perineural/lymphovascular invasion were independently associated with worse disease-free survival and overall survival. CONCLUSIONS In our cohort, the NLR did not correlate with survival outcomes in LARC patients undergoing neoadjuvant CRT. The prognostic value of NLR should be validated in large-scale prospective studies.