Association between nutritional status assessed by a digital self-administered tool (R+ dietitian) and clinicopathologic factors in cancer patients: A comprehensive analysis.

Objective: Malnutrition is prevalent among cancer patients, smartphone-based self-administered nutritional assessment tools offer a promising solution for effective nutritional screening. This study aims to retrospectively analyze the relationships between nutritional status evaluated by the digital tool (R+ Dietitian) and clinicopathologic factors of cancer patients. Methods: Cancer patients who met the inclusion criteria were divided into two subgroups based on age, Nutritional Risk Screening-2002, Patient-Generated Subjective Global Assessment Short Form, body mass index, and hospital stays for comparison. Correlation and regression analysis were used to comprehensively assess the relationship between nutritional status and clinicopathologic factors. Findings: A total of 535 hospitalized cancer patients (58.32 ± 11.24 years old) were recruited. Patients identified with nutritional risk assessed by R+ Dietitian were significantly older, had lower body weight, lower body mass index, greater weight loss, and longer hospital stays (all of above, P < 0.01). Multiple logistic regression analysis indicated that serum prealbumin concentration (odds ratio: 0.992, 95% confidence interval: 0.987-0.997, P = 0.001), weight loss (odds ratio: 7.309, 95% confidence interval: 4.026-13.270, P < 0.001), and body mass index < 18.5 (odds ratio: 5.882, 95% confidence interval: 2.695-12.821, P < 0.001) predicted nutritional risk indicated by Nutritional Risk Screening-2002 score ≥3. Hemoglobin concentration (odds ratio: 0.983, 95% confidence interval: 0.970-0.996, P = 0.011), weight (odds ratio: 1.111, 95% confidence interval: 1.056-1.169, P < 0.001), weight loss (odds ratio: 7.502, 95% confidence interval: 4.394-12.810, P < 0.001), body mass index (odds ratio: 0.661, 95% confidence interval: 0.564-0.775, P < 0.001), and energy intake (odds ratio: 0.996, 95% confidence interval: 0.995-0.997, P < 0.001) predicted nutritional risk indicated by Patient-Generated Subjective Global Assessment Short Form score ≥4. Multiple linear regression analysis revealed that Patient-Generated Subjective Global Assessment Short Form scores ≥3 (b = 2.032, P = 0.008) were significantly associated with longer hospital stays. Conclusions: The nutritional risks assessed by R+ Dietitian accurately reflected the characteristics of malnutrition in cancer patients and predicted hospital stay and cost, indicating the applicability of R+ Dietitian to improving the efficiency of nutritional management for cancer patients.

Photothermal-Starvation Therapy Nanomodulator Capable of Inhibiting Colorectal Cancer Recurrence and Metastasis by Energy Metabolism Reduction.

The recurrence and metastasis of colorectal cancer (CRC) have been considered as a severe challenge in clinical treatment. Recent studies have demonstrated that matrix metalloproteinases (MMPs) and lactate can promote local tumor angiogenesis, recurrence, and metastasis. The expression of MMPs is highly dependent on energy metabolism, and lactate is considered an alternative energy source for tumor proliferation and metastasis. Therefore, using a rational approach, a photothermal-starvation therapy nanomodulator that can reduce energy metabolism to suppress CRC recurrence and metastasis is designed. To design a suitable nanomodulator, glucose oxidase (GOX), indocyanine green (IR820), and α-cyano-4-hydroxycinnamic acid (CHC) into nanoparticles by a coassembly method are combined. The photothermal properties of IR820 provide the appropriate temperature and oxygen supply for the enzymatic reaction of GOX to promote intracellular glucose consumption. CHC inhibits the expression of monocarboxylate transporter 1 (MCT1), the transporter of lactic acid into cells, and also reduces oxygen consumption and promotes the GOX reaction. Additionally, altering adenosine triphosphate synthesis to block heat shock proteins expression can be an effective means to prevent IR820-mediated photothermal therapy resistance. Thus, this dual photothermal-starvation therapy nanomodulator efficiently suppresses the recurrence and metastasis of CRC by depleting intracellular nutrients.

Unmet needs for rehabilitation service of middle-aged and older adult residents in Chengdu, Sichuan, China: A cross-sectional study.

To investigate the unmet needs for rehabilitation services among middle-aged and older adults in Chengdu, Sichuan, China, and identify the associated factors. This cross-sectional study was conducted on middle-aged and older adults in Chengdu, Sichuan, China, between 2015 and 2016. The questionnaire included demographic data and questions about rehabilitation needs. Multivariable logistic regression analysis was used to identify the associated factors of unmet needs for rehabilitation services. Among 663 participants, 91.70% needed medical rehabilitation (608/663), 26.55% of who need auxiliary equipment (176/663), 77.07% of who need daily care and social participation (511/663), and 79.34% of who need recreational therapy activities (526/663), while < 30% required auxiliary equipment. Multivariate logistic regression analysis showed that residents who were married, had annual income < CNY 80,000, had no medical insurance, had three or more health problems, were aged ≥ 60, and the disability status were independently associated with unmet needs for rehabilitation services (all P < 0.05). Marital status, annual income, medical insurance, health problems, and disability might be factors independently associated with the unmet needs for rehabilitation services. Attention should be paid to the financial burden of the population on rehabilitation services, and in addition to the disabled, the slow patients should also be given priority.

RNF4 Regulates the BLM Helicase in Recovery From Replication Fork Collapse.

Sumoylation is an important enhancer of responses to DNA replication stress and the SUMO-targeted ubiquitin E3 ligase RNF4 regulates these responses by ubiquitylation of sumoylated DNA damage response factors. The specific targets and functional consequences of RNF4 regulation in response to replication stress, however, have not been fully characterized. Here we demonstrated that RNF4 is required for the restart of DNA replication following prolonged hydroxyurea (HU)-induced replication stress. Contrary to its role in repair of γ-irradiation-induced DNA double-strand breaks (DSBs), our analysis revealed that RNF4 does not significantly impact recognition or repair of replication stress-associated DSBs. Rather, using DNA fiber assays, we found that the firing of new DNA replication origins, which is required for replication restart following prolonged stress, was inhibited in cells depleted of RNF4. We also provided evidence that RNF4 recognizes and ubiquitylates sumoylated Bloom syndrome DNA helicase BLM and thereby promotes its proteosome-mediated turnover at damaged DNA replication forks. Consistent with it being a functionally important RNF4 substrate, co-depletion of BLM rescued defects in the firing of new replication origins observed in cells depleted of RNF4 alone. We concluded that RNF4 acts to remove sumoylated BLM from collapsed DNA replication forks, which is required to facilitate normal resumption of DNA synthesis after prolonged replication fork stalling and collapse.

[Qualitative study on working experience of COVID-19 care nurses].

OBJECTIVE: To study the working experience of COVID-19 care nurses. METHODS: Twenty two nurses taking care of COVID-19 patients were interviewed by means of descriptive phenomenology. All the data were transcribed and recorded, and then processed into WORD documents. The Colaizzi 7 footwork was used to classify, encode, establish nodes and extract themes based on Nvivo11.0 software. RESULTS: Two main themes were extracted: one is the positive feelings of nurses, including the sense of professional mission and pride, the sense of achievement and happiness, the improvement of self-worth and ability, the powerful support system and the power of role models; the other is the negative experience of nurses, including the worry and anxiety at work, the lack of experience and trust, the difficulty of work, and the inconvenience of isolating life. CONCLUSIONS: s While fully affirming the work value of nurses, it is necessary for the society, hospitals and patients to give extensive and continuous support, care and respect to nurses, so as to stimulate their working enthusiasm and sense of professional achievement. Hospital managers need to implement all kinds of security work, meet the safety needs of nurses, pay attention to the physical and mental health of nurses, strengthen the training of nursing talents for critical and severe diseases and infectious diseases, improve the allocation of human resources, and enhance the ability of material allocation and reserve for major health events, so as to make adequate preparations for coping with public health events in the future.

A retrospective analysis of allergic reaction severities and minimal eliciting doses for peanut, milk, egg, and soy oral food challenges.

Food allergy is a public health concern, affecting up to 6% of children and 2% of adults. The severity of allergic reactions can range from mild to potentially life-threatening. In addition, the minimum amount of protein needed to provoke an allergic reaction in an individual patient (the minimal eliciting dose (MED)) ranges from a few micrograms to several grams. To determine whether a retrospective analysis of published data from oral food challenges could be used to assess the potential relationship between MEDs and reaction severities at the MEDs, a three class (mild, moderate, severe) reaction grading system was developed by integrating previously published reaction grading systems. MEDs and symptoms were collected from food challenge studies and each reaction was graded using the integrated grading system. Peanut allergic patients who experienced severe reactions had significantly higher MEDs and threshold distribution doses than those who experienced mild and moderate reactions. No significant differences in threshold distributions according to the severity grading were found for milk, egg and soy. The relationship between threshold dose distribution and reaction severity based on these grading criteria differed between peanut and other allergens, and severe reactions were found to occur in some patients at low MEDs for all of these food allergens.

[Optimization of the extraction process of the effective components in fructus phyllanthi].

OBJECTIVE: To optimize the extraction process of the effective components in Fructus Phyllanthi. METHODS: Using Fructus Phyllanthi from Puning, Guangdong as the raw materials, its extraction process was screened by the orthogonal design. The extraction rates of polyphenol from Fructus Phyllanthi under different extraction conditions were compared to determine the optimum extraction technology. The effects of the ratio of raw materials to liquid, extraction time, extraction temperature and extraction number on extraction rates of polysaccharose in Fructus Phyllanthi were also investigated. RESULTS: The optimum extraction conditions for polyphenol were as follows: 50% methanol as solvent, ratio of raw materials to liquid 1:10, extraction times 1, extraction time 90 min. The optimum extracting conditions for polysaccharose were as follows: ratio of raw materials to liquid 1:20, extraction time 3.0 h, extraction times 3, and extraction temperature 90 degrees C. CONCLUSION: The optimization of the extraction process for polyphenol and polysaccharide in Fructus Phyllanthi has a good reference guide for further developing a seris of health care products of Fructus Phyllanthi.

Analysis of U.S. Food and Drug Administration food allergen recalls after implementation of the food allergen labeling and consumer protection act.

To avoid potentially life-threatening reactions, food allergic consumers rely on information on food labels to help them avoid exposure to a food or ingredient that could trigger a reaction. To help consumers in the United States obtain the information that they need, the Food Allergen Labeling and Consumer Protection Act of 2004 defined a major food allergen as being one of eight foods or food groups and any ingredient that contains protein from one of these foods or food groups. A food that contains an undeclared major food allergen is misbranded under the U.S. Food, Drug, and Cosmetic Act and is subject to recall. Food allergen labeling problems are the most common cause of recalls for U.S. Food and Drug Administration (FDA)-regulated food products. To help understand why food allergen recalls continue to occur at a high rate, information on each food allergen recall that occurred in fiscal years 2007 through 2012 was obtained from the FDA recall database. This information was analyzed to identify the food, allergen, root cause, and mode of discovery for each food allergen recall. Bakery products were the most frequently recalled food type, and milk was the most frequently undeclared major food allergen. Use of the wrong package or label was the most frequent problem leading to food allergen recalls. These data are the first reported that indicate the importance of label and package controls as public health measures.

RNF4-dependent hybrid SUMO-ubiquitin chains are signals for RAP80 and thereby mediate the recruitment of BRCA1 to sites of DNA damage.

The DNA repair function of the breast cancer susceptibility protein BRCA1 depends in part on its interaction with RAP80, which targets BRCA1 to DNA double-strand breaks (DSBs) through recognition of K63-linked polyubiquitin chains. The localization of BRCA1 to DSBs also requires sumoylation. We demonstrated that, in addition to having ubiquitin-interacting motifs, RAP80 also contains a SUMO-interacting motif (SIM) that is critical for recruitment to DSBs. In combination with the ubiquitin-binding activity of RAP80, this SIM enabled RAP80 to bind with nanomolar affinity to hybrid chains consisting of ubiquitin conjugated to SUMO. Furthermore, RNF4, a SUMO-targeted ubiquitin E3 ligase that synthesizes hybrid SUMO-ubiquitin chains, localized to DSBs and was critical for the recruitment of RAP80 and BRCA1 to sites of DNA damage. Our findings, therefore, connect ubiquitin- and SUMO-dependent DSB recognition, revealing that RNF4-synthesized hybrid SUMO-ubiquitin chains are recognized by RAP80 to promote BRCA1 recruitment and DNA repair.

SUMO modification regulates BLM and RAD51 interaction at damaged replication forks.

The gene mutated in Bloom's syndrome, BLM, is important in the repair of damaged replication forks, and it has both pro- and anti-recombinogenic roles in homologous recombination (HR). At damaged forks, BLM interacts with RAD51 recombinase, the essential enzyme in HR that catalyzes homology-dependent strand invasion. We have previously shown that defects in BLM modification by the small ubiquitin-related modifier (SUMO) cause increased gamma-H2AX foci. Because the increased gamma-H2AX could result from defective repair of spontaneous DNA damage, we hypothesized that SUMO modification regulates BLM's function in HR repair at damaged forks. To test this hypothesis, we treated cells that stably expressed a normal BLM (BLM+) or a SUMO-mutant BLM (SM-BLM) with hydroxyurea (HU) and examined the effects of stalled replication forks on RAD51 and its DNA repair functions. HU treatment generated excess gamma-H2AX in SM-BLM compared to BLM+ cells, consistent with a defect in replication-fork repair. SM-BLM cells accumulated increased numbers of DNA breaks and were hypersensitive to DNA damage. Importantly, HU treatment failed to induce sister-chromatid exchanges in SM-BLM cells compared to BLM+ cells, indicating a specific defect in HR repair and suggesting that RAD51 function could be compromised. Consistent with this hypothesis, RAD51 localization to HU-induced repair foci was impaired in SM-BLM cells. These data suggested that RAD51 might interact noncovalently with SUMO. We found that in vitro RAD51 interacts noncovalently with SUMO and that it interacts more efficiently with SUMO-modified BLM compared to unmodified BLM. These data suggest that SUMOylation controls the switch between BLM's pro- and anti-recombinogenic roles in HR. In the absence of BLM SUMOylation, BLM perturbs RAD51 localization at damaged replication forks and inhibits fork repair by HR. Conversely, BLM SUMOylation relieves its inhibitory effects on HR, and it promotes RAD51 function.

Small ubiquitin-related modifier (SUMO) binding determines substrate recognition and paralog-selective SUMO modification.

Small ubiquitin-related modifiers (SUMOs) regulate diverse cellular processes through their covalent attachment to target proteins. Vertebrates express three SUMO paralogs: SUMO-1, SUMO-2, and SUMO-3 (SUMO-2 and SUMO-3 are approximately 96% identical and referred to as SUMO-2/3). SUMO-1 and SUMO-2/3 are conjugated, at least in part, to unique subsets of proteins and thus regulate distinct cellular pathways. However, how different proteins are selectively modified by SUMO-1 and SUMO-2/3 is unknown. We demonstrate that BLM, the RecQ DNA helicase mutated in Bloom syndrome, is preferentially modified by SUMO-2/3 both in vitro and in vivo. Our findings indicate that non-covalent interactions between SUMO and BLM are required for modification at non-consensus sites and that preferential SUMO-2/3 modification is determined by preferential SUMO-2/3 binding. We also present evidence that sumoylation of a C-terminal fragment of HIPK2 is dependent on SUMO binding, indicating that non-covalent interactions between SUMO and target proteins provide a general mechanism for SUMO substrate selection and possible paralog-selective modification.

Repression of interferon-gamma expression in T cells by Prospero-related homeobox protein.

Interferon-gamma (IFN-gamma) is a major proinflammatory effector and regulatory cytokine produced by activated T cells and NK cells. IFN-gamma has been shown to play pivotal roles in fundamental immunological processes such as inflammatory reactions, cell-mediated immunity and autoimmunity. A variety of human disorders have now been linked to irregular IFN-gamma expression. In order to achieve proper IFN-gamma-mediated immunological effects, IFN-gamma expression in T cells is subject to both positive and negative regulation. In this study, we report for the first time the negative regulation of IFN-gamma expression by Prospero-related Homeobox (Prox1). In Jurkat T cells and primary human CD4+ T cells, Prox1 expression decreases quickly upon T cell activation, concurrent with a dramatic increase in IFN-gamma expression. Reporter analysis and chromatin immunoprecipitation (ChIP) revealed that Prox1 associates with and inhibits the transcription activity of IFN-,gammapromoter in activated Jurkat T cells. Co-immunoprecipitation and GST pull-down assay demonstrated a direct binding between Prox1 and the nuclear receptor peroxisome proliferator-activated receptor gamma (PPPARgamma, which is also an IFN-gamma repressor in T cells. By introducing deletions and mutations into Prox1, we show that the repression of IFN-gamma promoter by Prox1 is largely dependent upon the physical interaction between Prox1 and PPPARgamma Furthermore, PPPARgammaantagonist treatment removes Prox1 from IFN-gamma promoter and attenuates repression of IFN-gamma expression by Prox1. These findings establish Prox1 as a new negative regulator of IFN-gamma expression in T cells and will aid in the understanding of IFN-gamma transcription regulation mechanisms.

The coiled-coil domain of TRAF6 is essential for its auto-ubiquitination.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a crucial signaling transducer that regulates a diverse array of physiological processes, including adaptive immunity, innate immunity, and bone metabolism. Importantly, it is essential for activating NF-kappaB signaling pathway in response to interleukin-1 and Toll-like receptor ligands. Previously, we characterized TRAF6 to be a ubiquitin ligase. In combination with the ubiquitin conjugating enzyme complex Ubc13/Uev1A, TRAF6 could catalyze the formation on itself of unique Lys-63 linked polyubiquitin chain that positively regulated NF-kappaB signaling pathway. However, it remains unknown how this auto-ubiquitination process is regulated. In this study, we found that the coiled-coil domain of TRAF6 was essential for its auto-ubiquitination and activating NF-kappaB signaling pathway. This domain served not as the specific target where the polyubiquitin chain was linked, but as a specific bridge to recruit Ubc13/Uev1A.

Inhibition of SNAP-25 phosphorylation at Ser187 is involved in chronic morphine-induced down-regulation of SNARE complex formation.

Opiate abuse has been shown to cause adaptive changes in presynaptic release and protein phosphorylation-mediated synaptic plasticity, but the underlying mechanisms remain unclear. Neuronal SNARE proteins serve as important regulatory molecules underlying neural plasticity in view of their major role in the process of neurotransmitter release. In the present study, the expression of SNAP-25, a t-SNARE protein essential for vesicle release, was found to be dramatically regulated in hippocampus after chronic morphine treatment, which was visualized with two-dimensional gel electrophoresis. The spots of SNAP-25 in the gel were shifted along the dimension of isoelectric point, indicating a likely change of the post-transcriptional modification. Immunoblotting analysis with specific antibody to Ser187, a protein kinase C (PKC) phosphorylation site of SNAP-25, revealed that the specific phosphorylation was correspondingly decreased, which was correlated with morphine-induced inhibition of PKC activity. Moreover, the level of ternary complex of SNARE proteins in either synaptosomes or PC12 cells was significantly reduced after chronic morphine treatment. This suggests a causal relationship between the inhibition of PKC-dependent SNAP-25 phosphorylation and the down-regulation of SNARE complex formation after chronic morphine treatment. Further analysis of SNARE complex formed by transfection of the wild-type or Ser187 mutants of SNAP-25 showed that only wild-type-formed complex was inhibited by morphine treatment. Thus, these results indicate that chronic morphine treatment inhibits phosphorylation of SNAP-25 at Ser187 and leads to a down-regulation of SNARE complex formation, which presents a potential molecular mechanism for the alteration of exocytotic process and neural plasticity during opiate abuse.