Sorbitol induces flower bud formation via the MADS-box transcription factor EjCAL in loquat.

Sorbitol is an important signaling molecule in fruit trees. Here, we observed that sorbitol increased during flower bud differentiation (FBD) in loquat (Eriobotrya japonica Lindl.). Transcriptomic analysis suggested that bud formation was associated with the expression of the MADS-box transcription factor (TF) family gene, EjCAL. RNA fluorescence in situ hybridization showed that EjCAL was enriched in flower primordia but hardly detected in the shoot apical meristem. Heterologous expression of EjCAL in Nicotiana benthamiana plants resulted in early FBD. Yeast-one-hybrid analysis identified the ERF12 TF as a binding partner of the EjCAL promoter. Chromatin immunoprecipitation-PCR confirmed that EjERF12 binds to the EjCAL promoter, and ß-glucuronidase activity assays indicated that EjERF12 regulates EjCAL expression. Spraying loquat trees with sorbitol promoted flower bud formation and was associated with increased expression of EjERF12 and EjCAL. Furthermore, we identified EjUF3GaT1 as a target gene of EjCAL and its expression was activated by EjCAL. Function characterization via overexpression and RNAi reveals that EjUF3GaT1 is a biosynthetic gene of flavonoid hyperoside. The concentration of the flavonoid hyperoside mirrored that of sorbitol during FBD and exogenous hyperoside treatment also promoted loquat bud formation. We identified a mechanism whereby EjCAL might regulate hyperoside biosynthesis and confirmed the involvement of EjCAL in flower bud formation in planta. Together, these results provide insight into bud formation in loquat and may be used in efforts to increase yield.

Lymphocyte to C-reactive protein ratio could better predict the prognosis of patients with stage IV cancer.

BACKGROUND: Systemic inflammation is currently regarded as a hallmark of cancer. This study aimed to accurately clarify the prognostic value of various inflammatory markers in patients with stage IV cancer. METHODS: This study assessed 2,424 patients with cancer diagnosed with cancer in tumor, node, metastasis (TNM) stage IV. After evaluating the predictive value of 13 inflammatory indicators for patient prognosis using the C index, the lymphocyte C-reactive protein ratio (LCR) was selected to elucidate the prognostic and predictive values in patients with stage IV cancer. Kaplan-Meier and Cox proportional hazards regression models were used to analyze long-term survival. RESULTS: A total of 1,457 men (60.1%) and 967 women (39.9%) diagnosed with TNM stage IV cancer were enrolled. A ratio of 2,814 was defined as the optimal cut-off value for the LCR. The LCR was the most accurate prognosis predictor for patients with stage IV cancer among the 13 inflammatory nutritional markers evaluated. The multivariate-adjusted restricted cubic spline plot suggested that LCR had an L-shaped dose-response association with all-cause mortality risk. Patients with lower LCR levels tended to present with worse prognoses. Kaplan-Meier curves and log-rank test results showed that the high LCR groups (LCR ≥ 2,814) exhibited a better prognosis, whereas patients with stage IV cancer of different sex and tumor types (for example, gastrointestinal tumor, non-gastrointestinal tumor, and lung cancer) had a worse survival time. CONCLUSION: The LCR score can be regarded as a stable and useful biomarker to predict prognosis in patients with TNM stage IV compared to other evaluated inflammation indicators.

Which anthropometric measurement is better for predicting survival of patients with cancer cachexia?

No relevant studies have yet been conducted to explore which measurement can best predict the survival time of patients with cancer cachexia. This study aimed to identify an anthropometric measurement that could predict the 1-year survival of patients with cancer cachexia. We conducted a nested case-control study using data from a multicentre clinical investigation of cancer from 2013 to 2020. Cachexia was defined using the Fearon criteria. A total of 262 patients who survived less than 1 year and 262 patients who survived more than 1 year were included in this study. Six candidate variables were selected based on clinical experience and previous studies. Five variables, BMI, mid-arm circumference, mid-arm muscle circumference, calf circumference and triceps skin fold (TSF), were selected for inclusion in the multivariable model. In the conditional logistic regression analysis, TSF (P = 0·014) was identified as a significant independent protective factor. A similar result was observed in all patients with cancer cachexia (n 3084). In addition, a significantly stronger positive association between TSF and the 1-year survival of patients with cancer cachexia was observed in participants aged > 65 years (OR: 0·94; 95 % CI 0·89, 0·99) than in those aged ≤ 65 years (OR: 0·96; 95 % CI 0·93, 0·99; Pinteraction = 0·013) and in participants with no chronic disease (OR: 0·92; 95 % CI 0·87, 0·97) than in those with chronic disease (OR: 0·97; 95 % CI 0·94, 1·00; Pinteraction = 0·049). According to this study, TSF might be a good anthropometric measurement for predicting 1-year survival in patients with cancer cachexia.

PG-SGA SF in nutrition assessment and survival prediction for elderly patients with cancer.

BACKGROUND: This study was sought to report the prevalence of malnutrition in elderly patients with cancer. Validate the predictive value of the nutritional assessment tool (Patient-Generated Subjective Global Assessment Short Form, PG-SGA SF) for clinical outcomes and assist the therapeutic decision. METHODS: This is a secondary analysis of a multicentric, observational cohort study. Elderly patients with cancer older than 65 years were enrolled after the first admission. Nutritional status was identified using the PG-SGA SF. RESULTS: Of the 2724 elderly patients included in the analysis, 65.27% of patients were male (n = 1778); the mean age was 71.00 ± 5.36 years. 31.5% of patients were considered malnourished according to PG-SGA SF. In multivariate analysis, malnutrition(PG-SGA SF > 5) was significantly associated with worse OS (HR: 1.47,95%CI:1.29-1.68), affects the quality of life, and was related to more frequent nutrition impact symptoms. During a median follow-up of 4.5 years, 1176 death occurred. The mortality risk was 41.10% for malnutrition during the first 12 months and led to a rate of 323.98 events per-1000-patient-years. All nutritional assessment tools were correlated with each other (PG-SGA SF vs. PG-SGA: r = 0.98; PG-SGA SF vs. GLIM[Global Leadership Initiative on Malnutrition]: r = 0.48, all P < 0.05). PG-SGA SF and PG-SGA performed similarly to predict mortality but better than GLIM. PG-SGA SF improves the predictive ability of the TNM classification system for mortality in elderly patients with cancer, including distinguishing patients' prognoses and directing immunotherapy. CONCLUSIONS: The nutritional status as measured by PG-SGA SF which is a prognostic factor for OS in elderly cancer patients and could improve the prognostic model of TNM.

Survey and analysis of the nutritional status in hospitalized patients with malignant gastric tumors and its influence on the quality of life.

BACKGROUND/OBJECTIVES: The assessment of nutritional status and the quality of life in patients with gastric cancer has become one of the important goals of current clinical treatment. The purpose of this study was to assess the nutritional status in hospitalized gastric cancer patients by using patient-generated subjective global assessment (PG-SGA) and to analyze the influence of nutritional status on the patients' quality of life (QOL). METHODS: We reviewed the pathological diagnosis of gastric cancer for 2322 hospitalized patients using PG-SGA to assess their nutritional status and collected data on clinical symptoms, the anthropometric parameters (height, weight, body mass index (BMI), mid-arm circumference (MAC), triceps skin-fold thickness (TSF), and hand-grip strength (HGS). We also collected laboratory data (prealbumin, albumin, hemoglobin) within 48 h after the patient was admitted to the hospital. The 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) was used for QOL assessment in all patients. RESULTS: By using PG-SGA, we found 80.4% of the patients were malnourished (score ≥ 4) and 45.1% of the patients required urgent nutritional support (score ≥ 9). In univariate analysis, old age (> 65 years, p < 0.001), female (p = 0.007), residence in a village (p = 0.004), a lower level of education (p < 0.001), and self-paying (p < 0.001) were indicated as risk factors of patients with gastric cancer to be suffering from severe malnutrition. There was a negative correlation between PG-SGA and various nutritional parameters (p < 0.05). The quality of life was significantly different in gastric cancer patients with different nutritional status (p < 0.01). CONCLUSION: Malnutrition of hospitalized patients with gastric cancer in China is common and seriously affects the patients' quality of life. The nutritional status should be evaluated in a timely manner and reasonable nutritional intervention should be provided as soon as possible. The PG-SGA was fit for using as a clinical nutrition assessment method, being worthy of clinical application.

[Application of the Green Model to lifestyle intervention in male sterility patients].

OBJECTIVE: To evaluate the application of the Green Model to lifestyle intervention in male infertility patients. METHODS: A total of 120 male infertility patients treated from October 2018 to January 2019 were equally randomized into a control and an observation group, the former given conventional nursing and the latter Green Model intervention in addition. Comparisons were made between the two groups of patients in their satisfaction with nursing intervention, scores on lifestyle knowledge, beliefs and behaviors, and compliance with the healthy lifestyle. RESULTS: The patients in the observation group showed a dramatically higher satisfaction with the nursing intervention than the controls (96.67% vs 75.00%, P < 0.01) as well as higher scores on lifestyle knowledge (8.92 ± 1.08 vs 5.89 ± 1.99, P < 0.05), beliefs (8.78 ± 0.68 vs 5.98 ± 1.50, P < 0.05) and behaviors (19.32 ± 1.12 vs 13.88 ± 2.11, P < 0.05) and their compliance with the healthy lifestyle (61.67% vs 38.33, P < 0.05). CONCLUSIONS: Green Model intervention can help male infertility patients to obtain correct lifestyle cognition, beliefs and behaviors, promote their compliance with the healthy lifestyle and improve their satisfaction with nursing intervention.

Association Between Serum C-Reactive Protein Concentration and Nutritional Status of Malignant Tumor Patients.

BACKGROUND: The level of the systemic inflammatory marker C-reactive protein (CRP) is elevated in many patients with malignant disease and may be related to nutritional status. OBJECTIVE: To analyze the association between serum CRP levels in patients with malignant tumors and their nutritional status. METHOD: A total of 3,692 cases were analyzed and the serum CRP levels were determined using an immunometric assay. Nutritional status was assessed by using patient-generated subjective global assessment (PG-SGA). The biochemical evaluation of prealbumin (PA), albumin (ALB), cholesterol (CHOL), and triglycerides (TG) were assayed within 48 h admission to the hospital. The association between serum CRP concentration and the nutritional status, the stage of the tumor and other factors was analyzed by univariate and multivariate logistic regression analysis. RESULT: Elevated serum CRP was observed in 47.6% (1,548/3,269) of patients compared with the reference value, and the median CRP concentration was 18.29 mg/l. Patient serum CRP concentrations in the malnourished group (PG-SGA B + C) were higher than in the well-nourished (PG-SGA A) patients (P < 0.05). The serum CRP level was related to the patients' age, gender, tumor stage, and was affected by hepatitis, liver cirrhosis, diabetes, but it has no effect on hypertension. The CRP high patients had lower PA and ALB levels, lower Karnofsky performance status scores, and higher PG-SGA scores (P < 0.05), and there was no relationship with CHOL and TG levels. Weight loss in the previous 1 mo was seen with CRP positive patients (P < 0.05). CONCLUSION: Almost 50% of malignant tumor patients had elevated serum CRP levels indicating a systemic inflammatory state. The nutritional status was worse in cancer patients with higher concentrations of serum CRP. The level of CRP was associated with the tumor stage, and, as stage is a prognostic factor, so can CRP be used as a prognostic maker in malignant tumors patients.

Comparative transcriptome profiling of freezing stress responses in loquat (Eriobotrya japonica) fruitlets.

Loquat (Eriobotrya japonica Lindl.) is an important subtropical, commercial fruit in China. It blossoms during autumn and winter in most areas of China and its fruitlets usually suffer from freezing stress. However, studies about the mechanisms underlying freezing stress in loquat are very limited. The gene expression profiles of loquat fruitlets subjected to freezing (G2 library) versus non-treated ones (G1 library) were investigated using Illumina sequencing technology to elucidate the molecular mechanisms and identify the genes that play vital roles in the freezing stress response. The results showed that approximately 157.63 million reads in total were obtained from freeze-treated and non-treated loquat fruitlets. These reads were assembled into 87,379 unigenes with an average length of 710 bp and an N50 of 1,200 bp. After comparing the profiles obtained from the G1 and G2 libraries, 2,892 differentially expressed genes were identified, of which 1,883 were up-regulated and 1,009 were down-regulated in the treated samples compared to non-treated ones. These unigenes showed significant differences in expression for carbohydrate transport and metabolism, amino acid metabolism, energy metabolism, and lipid metabolism, which are involved in defense against freezing stress. Glycolysis/gluconeogenesis was one of the most significantly regulated pathways. Freezing also significantly damaged the membrane system of loquat fruitlets, and several defense mechanisms were induced. Some selected genes related to low temperature resistance were validated by quantitative real-time PCR (qRT-PCR). The results revealed many genes and pathways that are part of freezing resistance processes and expand our understanding of the complex molecular events involved in freezing stress.

[Flavanoids Extracted from Onion Inhibited Activation of Microglia and Release of Proinflammatory Factors around the Hematoma in ICH Model Rats].

OBJECTIVE: To study flavanoids extracted from onion (FEO) on the number of activated microglia and the release of proinflammatory factors in intracerebral hemorrhage (ICH) model rat at different time points, and to explore its possible mechanism for treating ICH. METHODS: Totally 100 Wistar rats were used for preparing ICH model, and ICH model was successfully established in 90 of them. The 90 rats were randomly divided into the sham-operation group (n =10) , the ICH group (n =40) , the FEO group (n =40). Totally 100 [L autoblood was injected from fixed position to rats in the ICH group and the FEO group during modeling. Meanwhile, FEO at 0. 2 mL/10 g was given to rats in the FEO group, twice daily. No drug intervention was given to rats in the ICH group and the sham-operation group. Each group was further sub-divided into 5 sub-groups according to different time points such as 6, 24, 48, 72 h, and 7 days. There were 8 rats in each sub-group of the ICH group and the FEO group, 10 groups in total. There were 2 rats in each subgroup of the sham-operation group, 5 groups in total. Neurological functions at different time points were observed by Garcia JH. The injury degree of brain tissue was observed at dif- ferent time points using HE staining. Activated microglia around hematoma were observed at different time points after ICH by using immunohistochemical staining. Expressions of TNF-α and IL-1 ß at different time points after ICH was detected using ELISA. RESULTS: In the ICH group, degenerated and necrotic zone occurred around hematoma after injecting autoblood, cells were untidily arranged with irregular nucleus, partial nucleus were shrunken with lamellar interstitial edema of the medulla. As time went by, degenerated and necrotic zone was dilated; vacant zone occurred around cells; cells were unevenly distributed with reduced neuron numbers. Meanwhile, infiltration of lymphocytes and neutrophils occurred. In the FEO group after FEO intervention, necrotic cells were lesser, cell arrangement and nucleus morphology were obviously alleviated, and infiltration of inflammatory cells was reduced at corresponding time points. Compared with the sham-operation group, behavioral scores at 5 time points all decreased, the number of activated microglia was added, and expressions of TNF-α and IL-1 ß in hematoma tissue increased in the ICH group (P <0. 01). Compared with the ICH group, behavioral scores at 48 and 72 h, as well as day 7 all increased, the number of activated microglia was reduced, and expressions of TNF-α and IL-1ß in hematoma tissue decreased in the FEO group (P <0. 01). CONCLUSION: FEO using the ethanol reflux method could improve symptoms of ICH model rats possibly by inhibiting activation of microolia and the release of proinflammatory factors around the hematoma.

Integrated neutrophil-to-lymphocyte ratio and handgrip strength better predict survival in patients with cancer cachexia.

OBJECTIVES: Systemic inflammation and skeletal muscle strength play crucial roles in the development and progression of cancer cachexia. In this study we aimed to evaluate the combined prognostic value of neutrophil-to-lymphocyte ratio (NLR) and handgrip strength (HGS) for survival in patients with cancer cachexia. METHODS: This multicenter cohort study involved 1826 patients with cancer cachexia. The NLR-HGS (NH) index was defined as the ratio of neutrophil-to-lymphocyte ratio to handgrip strength. Harrell's C index and receiver operating characteristic (ROC) curve analysis were used to assess the prognosis of NH. Kaplan-Meier analysis and Cox regression models were used to evaluate the association of NH with all-cause mortality. RESULTS: Based on the optimal stratification, 380 women (NH > 0.14) and 249 men (NH > 0.19) were classified as having high NH. NH has shown greater predictive value compared to other indicators in predicting the survival of patients with cancer cachexia according to the 1-, 3-, and 5-y ROC analysis and Harrell's C index calculation. Multivariate survival analysis showed that higher NH was independently associated with an increased risk of death (hazard ratio = 1.654, 95% confidence interval = 1.389-1.969). CONCLUSION: This study demonstrates that the NH index, in combination with NLR and HGS, is an effective predictor of the prognosis of patients with cancer cachexia. It can offer effective prognosis stratification and guidance for their treatment.

Discovery of distinct cancer cachexia phenotypes using an unsupervised machine-learning algorithm.

OBJECTIVES: Cancer cachexia is a debilitating condition with widespread negative effects. The heterogeneity of clinical features within patients with cancer cachexia is unclear. The identification and prognostic analysis of diverse phenotypes of cancer cachexia may help develop individualized interventions to improve outcomes for vulnerable populations. The aim of this study was to show that the machine learning-based cancer cachexia classification model generalized well on the external validation cohort. METHODS: This was a nationwide multicenter observational study conducted from October 2012 to April 2021 in China. Unsupervised consensus clustering analysis was applied based on demographic, anthropometric, nutritional, oncological, and quality-of-life data. Key characteristics of each cluster were identified using the standardized mean difference. We used logistic and Cox regression analysis to evaluate 1-, 3-, 5-y, and overall mortality. RESULTS: A consensus clustering algorithm was performed for 4329 patients with cancer cachexia in the discovery cohort, and four clusters with distinct phenotypes were uncovered. From clusters 1 to 4, the clinical characteristics of patients showed a transition from almost unimpaired to mildly, moderately, and severely impaired. Consistently, an increase in mortality from clusters 1 to 4 was observed. The overall mortality rate was 32%, 40%, 54%, and 68%, and the median overall survival time was 21.9, 18, 16.7, and 13.6 mo for patients in clusters 1 to 4, respectively. Our machine learning-based model performed better in predicting mortality than the traditional model. External validation confirmed the above results. CONCLUSIONS: Machine learning is valuable for phenotype classifications of patients with cancer cachexia. Detection of clinically distinct clusters among cachexic patients assists in scheduling personalized treatment strategies and in patient selection for clinical trials.

Activation of nuclear factor erythroid 2-related factor 2 and PPARγ plays a role in the genistein-mediated attenuation of oxidative stress-induced endothelial cell injury.

We investigate the cytoprotective effects and the molecular mechanism of genistein in oxidative stress-induced injury using an endothelial cell line (EA.hy926). An oxidative stress model was established by incubating endothelial cells with H2O2. According to the present results, genistein pretreatment protected endothelial cells against H2O2-induced decreases in cell viability and increases in apoptosis. Genistein also prevented the inhibition of B-cell lymphoma 2 and the activation of caspase-3 induced by H2O2. Genistein increased superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels and attenuated the decrease in these antioxidants during oxidative stress. We also found that genistein induced the promoter activity of both nuclear factor erythroid 2-related factor 2 (Nrf2) and PPARγ. Additionally, genistein induced the nuclear translocation of Nrf2 and PPARγ. While genistein caused the up-regulation of both Nrf2 and PPARγ, it also activated and up-regulated the protein expression and transcription of a downstream protein, haem oxygenase-1 (HO-1). Moreover, the use of Nrf2 small interfering RNA transfection and HO-1- or PPARγ-specific antagonists (Znpp and GW9662, respectively) blocked the protective effects of genistein on endothelial cell viability during oxidative stress. Therefore, we conclude that oxidative stress-induced endothelial cell injury can be attenuated by treatment with genistein, which functions via the regulation of the Nrf2 and PPARγ signalling pathway. Additionally, the endogenous antioxidants SOD, CAT and GSH appear to play a role in the antioxidant activity of genistein. The present findings suggest that the beneficial effects of genistein involving the activation of cytoprotective antioxidant genes may represent a novel strategy in the prevention and treatment of cardiovascular endothelial damage.

Nutrition-inflammation marker enhances prognostic value to ECOG performance status in overweight or obese patients with cancer.

BACKGROUND: Overweight or obese cancer patients are more likely to develop a proinflammatory status. The aim of this study was to investigate whether the nutrition-inflammation marker can provide additional prognostic information on top of well-established Eastern Cooperative Oncology Group performance status (ECOG-PS) in overweight or obese patients with cancer. METHODS: A total of 1667 overweight or obese cancer patients were enrolled in this study. We assessed the prediction accuracy of 10 nutrition-inflammation markers by time-dependent receiver operating characteristic (ROC) and elucidated their association with overall survival by the Kaplan-Meier method and a Cox model. RESULTS: In this analysis, the majority of patients had a good performance status (ECOG-PS score ≤1; 88.3%). Both the area under ROC curves and the C-index of the lymphocyte-C-reactive protein ratio (LCR) demonstrated that LCR was the most significant nutrition-inflammation marker correlated with survival. In patients with good ECOG-PS, a low LCR was significantly associated with poorer prognosisand enhanced the predictive ability of one-year mortality. For specific tumor types, a low LCR was an independent prognostic factor for lung cancer, upper gastrointestinal cancer, and colorectal cancer, and it tended to be a significant predictor for breast cancer. In addition, those patients with a combined low LCR and poorer ECOG-PS (ECOG-PS score >1) showed the worst prognosis. CONCLUSION: The LCR is more strongly associated with overall survival than other nutrition-inflammation markers, and it is able to further detect patients with worse prognosis on top of ECOG-PS in overweight or obese patients with cancer.

Sarcopenia prevalence in patients with cancer and association with adverse prognosis: A nationwide survey on common cancers.

OBJECTIVE: Although previous studies have implicated the negative outcomes of sarcopenia, evidence is limited to one or a few types of cancer. The aim of this study was to evaluate the distribution and influencing factors of sarcopenia, and explore the relationship between sarcopenia and cancer prognosis in a large oncological population. METHODS: This observational cohort study included patients diagnosed with malignant cancer between May 2011 and January 2019. Hematologic and anthropometric parameters were collected prospectively. Low skeletal muscle mass and radiodensity were diagnosed using clinical indicators, according to the two prediction models. The importance of potential risk factors for sarcopenia was estimated by subtracting the predicted degrees of freedom from the partial χ2 statistic. Hazard rates of death were calculated using the hazard function and Cox regression analyses. RESULTS: We included 13 761 patients with cancer; the prevalence of sarcopenia was 33%. The median age was 58 y and 7135 patients (52%) were men. Patients with sarcopenia had a worse nutritional status and quality of life than those without sarcopenia. Age was the most important risk factor for sarcopenia compared with body mass index or TNM stage. Additionally, patients with sarcopenia had a significantly higher and earlier peak risk for mortality. After adjusting for baseline characteristics, sarcopenia was independently associated with mortality in the research population (hazard ratio, 1.429; P < 0.001) and most cancer types. CONCLUSION: Age is the most important risk factor for sarcopenia even in patients with cancer. Sarcopenia is strongly associated with a poor quality of life and reduced overall survival.

AIWW: a new nutrition-screening tool for the oncologic population.

Malnutrition is a common comorbidity among patients with cancer. However, no nutrition-screening tool has been recognized in this population. A quick and easy screening tool for nutrition with high sensitivity and easy-to-use is needed. Based on the previous 25 nutrition-screening tools, the Delphi method was made by the members of the Chinese Society of Nutritional Oncology to choose the most useful item from each category. According to these results, we built a nutrition-screening tool named age, intake, weight, and walking (AIWW). Malnutrition was defined based on the scored patient-generated subjective global assessment (PG-SGA). Concurrent validity was evaluated using the Kendall tau coefficient and kappa consistency between the malnutrition risks of AIWW, nutritional risk screening 2002 (NRS-2002), and malnutrition screening tool (MST). Clinical benefit was calculated by the decision curve analysis (DCA), integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). A total of 11,360 patients (male, n=6,024 (53.0%) were included in the final study cohort, and 6,363 patients had malnutrition based on PG-SGA. Based on AIWW, NRS-2002, and MST, 7,545, 3,469, and 1,840 patients were at risk of malnutrition, respectively. The sensitivities of AIWW, NRS-2002, and MST risks were 0.910, 0.531, and 0.285, and the specificities were 0.768, 0.946, and 0.975. The Kendall tau coefficients of AIWW, NRS-2002, and MST risks were 0.588, 0.501, and 0.326, respectively. The area under the curve of AIWW, NRS-2002, and MST risks were 0.785, 0.739, and 0.630, respectively. The IDI, cNRI, and DCA showed that AIWW is non-inferior to NRS-2002 (IDI: 0.002 (-0.009, 0.013), cNRI: -0.015 (-0.049, 0.020)). AIWW scores can also predict the survival of patients with cancer. The missed diagnosis rates of AIWW, NRS-2002, and MST were 0.09%, 49.0%, and 73.2%, respectively. AIWW showed a better nutrition-screening effect than NRS-2002 and MST for patients with cancer and could be recommended as an alternative nutrition-screening tool for this population.

Enhancement of diastereoselectivity in photodimerization of alkyl 2-naphthoates with chiral auxiliaries via inclusion within γ-cyclodextrin cavities.

Irradiations of alkyl 2-naphthoates are known to result in four isomeric "cubane-like" photodimers: anti(HH)-2, syn(HH)-2, anti(HT)-2, and syn(HT)-2 where the anti(HH)-2, anti(HT)-2, and syn(HT)-2 consist of pairs of diastereomers. Here, chiral auxiliary and chiral microreactor strategies have been combined to achieve high diastereoselectivity in photodimerizations of an enantiomeric pair of 2-naphthoates with (R)- and (S)-1-methoxycarbonylethyl esters as chiral auxiliaries (1R and 1S). Thus, irradiations of their γ-cyclodextrin (γ-CD) complexes have been conducted. Fluorescence, IR, and NMR spectra of both enantiomers of 1 demonstrate that their γ-CD complexes are mainly 2:2 with the molecules of 1 in head-to-head orientations. Irradiation of the complexes in the solid state mainly resulted in anti(HH)-2. The absolute configuration of each diastereomer of anti(HH)-2 has been established for the first time here. The diastereomeric excesses (de's) of anti(HH)-2 from 1R and 1S were 94% and 86%, respectively. These de's are much higher than those found from irradiations in solution (55% for 1R and 1S), where the opposite diastereomeric form is in excess! Calculations of the energies of various conformations of the head-to-head 2:2 inclusion complexes were performed using the PM3 approach. The predicted major diastereomers based on the calculation are consistent with those found experimentally.

Glycyrrhizin protects rat heart against ischemia-reperfusion injury through blockade of HMGB1-dependent phospho-JNK/Bax pathway.

AIM: Glycyrrhizin (GL) has been found to inhibit extracellular HMGB1 cytokine's activity, and protect spinal cord, liver and brain against I/R-induced injury in experimental animals. The purpose of this study was to investigate the protective effect of GL in rat myocardial I/R-induced injury and to elucidate the underlying mechanisms. METHODS: Male adult Sprague-Dawley rats underwent a 30-min left coronary artery occlusion followed by a 24-h reperfusion. The rats were treated with glycyrrhizin or glycyrrhizin plus recombinant HMGB1 after 30 min of ischemia and before reperfusion. Serum HMGB1, TNF-α and IL-6 levels, and hemodynamic parameters were measured at the onset and different time points of reperfusion. At the end of the experiment, the heart was excised, and the infarct size and histological changes were examined. The levels of Bcl2, Bax and cytochrome c, as well as phospho-ERK1/2, phospho-JNK and phospho-P38 in the heart tissue were evaluated using Western blot analysis, and myocardial caspase-3 activity was measured colorimetrically using BD pharmingen caspase 3 assay kit. RESULTS: Intravenous administration of GL (10 mg/kg) significantly reduced the infarct size, but did not change the hemodynamic parameters at different time points during reperfusion. GL significantly decreased the levels of serum HMGB1, TNF-α and IL-6. GL changed the distribution of Bax and cytochrome c expression between the mitochondrial and cytosolic fractions in the heart tissue, resulting in inhibition of myocardial apoptosis. Moreover, expression of phospho-JNK, but not ERK1/2 and P38 was decreased by GL in the heart tissue. All of the effects produced by GL treatment were reversed by co-administration with the recombinant HMGB1 (100 µg). Intravenous administration of SP600125, a selective phospho-JNK inhibitor (0.5 mg/kg), attenuated HMGB1-dependent Bax translocation and the subsequent apoptosis. CONCLUSION: These results demonstrate that GL alleviates rat myocardial I/R-induced injury via directly inhibiting extracellular HMGB1 cytokine activity and blocking the phospho-JNK/Bax pathway.

Reference values of low body mass index, mid-upper arm circumference, and calf circumference in cancer patients: A nationwide multicenter observational study.

OBJECTIVE: Anthropometric measurements including body mass index (BMI), mid-upper arm circumference (MUAC), and calf circumference (CC) are simple and convenient indicators of nutritional status and muscle mass. However, most of their reference values come from studies based on healthy Western populations. The optimal reference values of these anthropometric factors in Asian patients with cancer are unclear. The aim of this study was to develop reference values of severely and moderately low BMI, MUAC, and CC by analyzing a large sample of patients with cancer from a nationwide population. METHODS: We conducted a retrospective analysis of 16 104 patients who were diagnosed with malignant diseases from June 2012 to January 2019. The median age of the patients was 58 y, and 52.5% were men. Optimal stratification was used to calculate reference values using X-tile software. Kaplan-Meier and multivariate Cox analysis were performed to analyze survival data. A receiver operating characteristic analysis was conducted to test the performance of new reference values in diagnosing malnutrition. RESULTS: The optimal reference values were calculated for BMI (moderately low: 19.7 [women] and 19 [men]; severely low: 16.7 [women] and 16.7 [men]), MUAC (moderately low: 24.5 [women] and 23.2 [men] severely low: 20.6 [women] and 19.4 [mnen]), and CC (moderately low: 29.1 [women] and 29.3 [men]; severely low: 26.7 [women] and 26.9 [men]). New reference values had more significant affects on mortality risk and better performance in predicting malnutrition than existing ones. CONCLUSIONS: The present study defined reference values of moderately and severely low BMI, MUAC, and CC, which showed strong associations with quality of life, malnutrition, and mortality risk. New reference values from the present study are classification references specifically for the Asian population, which is a new step to promote the application of Global Leadership Initiative on Malnutrition criteria and its severity grading system in Asia.

Identification of the major photodegradant in metronidazole by LC-PDA-MS and its reveal in compendial methods.

Metronidazole in aqueous solution is sensitive to light and UV irradiation, leading to the formation of N-(2-hydroxyethyl)-5-methyl-l,2,4-oxadiazole-3-carboxamide. This is revealed here by liquid chromatography with tandem photo diode array detection and mass spectrometry (LC-PDA-MS) and further verified by comparison with the corresponding reference substance and proton nuclear magnetic resonance (1H-NMR). However, in current compendial tests for related substances/organic impurities of metronidazole, the above photolytic degradant could not be detected. Thus, when photodegradation of metronidazole occurs, it could not be demonstrated. In our study, an improved LC method was developed and validated, which includes a detection at a wavelength of 230 nm and optimization of mobile phase composition thereby a better separation was obtained.

Value of the Controlling Nutritional Status score in predicting the prognosis of patients with lung cancer: A multicenter, retrospective study.

BACKGROUND: The body's immune-nutrition status affects prognosis in patients with lung cancer. The Controlling Nutritional Status (CONUT) score is an immune-nutrition-related index associated with prognosis in other tumors. We aimed to assess the value of CONUT scores in predicting prognosis in patients with lung cancer. METHODS: In this retrospective, multicenter study, 1339 patients with lung cancer were divided into low and high CONUT score groups. The relationship between CONUT scores and overall survival (OS) was assessed by survival curves and Cox proportional hazards regression modeling. A nomogram, including CONUT scores and other clinical variables, was established. RESULTS: There were 659 (49.2%; mean age, 59.91 years) low and 680 (50.8%; mean age, 62.23 years) high CONUT score patients. OS was significantly worse in patients with high than in those with low CONUT scores (P < 0.001), even after stratification by pathological types (non-small-cell lung cancer and small-cell lung cancer) and Tumor, Node, Metastasis (TNM) stages. A high CONUT score independently predicted risk in patients with lung cancer (adjusted hazard ratio, 1.48; 95% CI, 1.26-1.73; P < 0.001). The CONUT-based nomogram could predict prognosis well (C-index, 0.701), with better resolution and accuracy than TNM staging for predicting OS at 1, 2, and 3 years (area under the receiver operating characteristic curve, 0.735 vs 0.678, 0.742 vs 0.696, and 0.768 vs 0.743, respectively). CONCLUSION: The CONUT score can predict prognosis in patients with lung cancer. A CONUT-based nomogram can improve the accuracy of survival prediction in such patients.