Poor nutritional status is associated with the severity of omicron infection in the older adults.

BACKGROUND: The Omicron wave of Coronavirus disease 2019 (COVID-19) remains the dominant strain worldwide. The studies of nutritional status in geriatric people with COVID-19 Omicron variant are limited. Thus, the aim of this study was to investigate the incidence of poor nutritional status among Omicron infected older patients, and to explore the correlation between the nutritional status and the severity of Omicron infection in older patients. METHODS: This is a retrospective cross-sectional study. According to the clinical symptoms, patients were divided into two groups: mild and moderate to severe. Mini Nutritional Assessment short-form (MNA-SF) was conducted when patients were admitted and poor nutritional status was defined as MNA-SF score of 0-11. The inflammatory markers including neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and systemic inflammatory index (SII) were calculated and compared between two groups. RESULTS: Total of 324 patients were enrolled, with median [interquartile range (IQR)] age of 73 (17) years. Overall, 241 cases were mild, 83 cases were moderate to severe at the time of diagnosis and that 54.3% of patients had poor nutritional status. Patients with poor nutritional status were found to be older (P < 0.001) and less vaccinated (P < 0.001), with a longer virus shedding duration (P = 0.022), more comorbidities (≥ 2) (P = 0.004) and higher value of NLR (P < 0.001), PLR (P < 0.001) and SII (P = 0.012). Vaccination, cycle threshold value in ORF1ab gene (OR CT value) and female, higher MNA-SF score was negatively connected with probability of moderate to severe infection. For every 1 score increase in MNA-SF, the odds ratio of moderate to severe infection decreased by 14.8% [adjusted odds ratio (aOR), 0.852; 95% confidence interval (CI): 0.734-0.988; P = 0.034]. CONCLUSIONS: Older patients with poor nutritional status are more likely to develop moderate to severe Omicron infection.

The association of dietary inflammatory potential with sarcopenia in Chinese community-dwelling older adults.

BACKGROUND: Dietary-induced inflammation is potentially associated with sarcopenia. Nevertheless, few studies have investigated the structure of the inflammatory diet and its correlation with muscle function and performance in both the upper and lower limbs. This study was performed to explore the association of the dietary inflammatory index (DII) with sarcopenia and its diagnostic parameters. METHODS: We conducted a cross-sectional survey on a sample of 515 Chinese community-dwelling older adults selected through multistage cluster sampling from three districts in Shanghai. DII scores were calculated using a validated food frequency questionnaire. Sarcopenia and its diagnostic parameters were determined based on the definition set by the Asian Working Group on Sarcopenia (AWGS). RESULTS: The mean age of study participants was 71.31 ± 4.71 years. The prevalence of sarcopenia in the cohort was 12.4%. Older adults in the highest DII quartile had a 3.339 times increased risk of sarcopenia compared to those in the lowest quartile (OR Quartile4vs1:3.339, 95%CI: 1.232, 9.052, p-trend: 0.004) after adjusting for confounding factors. Additionally, a more pro-inflammatory diet was associated with lower appendicular skeletal muscle index (ASMI) (OR Quartile4vs1: 3.005, 95%CI: 1.275, 7.318, p-trend: 0.005), a higher 5-times sit-stand test time score (OR Quartile4vs1: 4.942, 95%CI: 1.745, 13.993, p-trend: 0.005), and lower gait speed (OR Quartile4vs1: 2.392, 95%CI: 1.104, 5.185, p-trend: 0.041) after adjusting for confounding factors. However, there was no significant association between DII, handgrip strength, and Short Physical Performance Battery (SPPB) score in either the unadjusted or adjusted model. CONCLUSION: This study found that the association between consuming a more pro-inflammatory diet and sarcopenia in Chinese community-dwelling older adults was mainly due to underlying low intakes of dietary energy, protein, and anti-inflammatory foods, and not due to the high intake of pro-inflammatory foods. Meanwhile, DII was more highly correlated with lower limb muscle strength and performance compared to upper limb muscle strength.

Creation of an ustekinumab external control arm for Crohn's disease using electronic health records data: A pilot study.

BACKGROUND: Randomized trials are the gold-standard for clinical evidence generation, but they can sometimes be limited by infeasibility and unclear generalizability to real-world practice. External control arm (ECA) studies may help address this evidence gaps by constructing retrospective cohorts that closely emulate prospective ones. Experience in constructing these outside the context of rare diseases or cancer is limited. We piloted an approach for developing an ECA in Crohn's disease using electronic health records (EHR) data. METHODS: We queried EHR databases and manually screened records at the University of California, San Francisco to identify patients meeting the eligibility criteria of TRIDENT, a recently completed interventional trial involving an ustekinumab reference arm. We defined timepoints to balance missing data and bias. We compared imputation models by their impacts on cohort membership and outcomes. We assessed the accuracy of algorithmic data curation against manual review. Lastly, we assessed disease activity following treatment with ustekinumab. RESULTS: Screening identified 183 patients. 30% of the cohort had missing baseline data. Nonetheless, cohort membership and outcomes were robust to the method of imputation. Algorithms for ascertaining non-symptom-based elements of disease activity using structured data were accurate against manual review. The cohort consisted of 56 patients, exceeding planned enrollment in TRIDENT. 34% of the cohort was in steroid-free remission at week 24. CONCLUSION: We piloted an approach for creating an ECA in Crohn's disease from EHR data by using a combination of informatics and manual methods. However, our study reveals significant missing data when standard-of-care clinical data are repurposed. More work will be needed to improve the alignment of trial design with typical patterns of clinical practice, and thereby enable a future of more robust ECAs in chronic diseases like Crohn's disease.

The scalable precision medicine open knowledge engine (SPOKE): a massive knowledge graph of biomedical information.

MOTIVATION: Knowledge graphs (KGs) are being adopted in industry, commerce and academia. Biomedical KG presents a challenge due to the complexity, size and heterogeneity of the underlying information. RESULTS: In this work, we present the Scalable Precision Medicine Open Knowledge Engine (SPOKE), a biomedical KG connecting millions of concepts via semantically meaningful relationships. SPOKE contains 27 million nodes of 21 different types and 53 million edges of 55 types downloaded from 41 databases. The graph is built on the framework of 11 ontologies that maintain its structure, enable mappings and facilitate navigation. SPOKE is built weekly by python scripts which download each resource, check for integrity and completeness, and then create a 'parent table' of nodes and edges. Graph queries are translated by a REST API and users can submit searches directly via an API or a graphical user interface. Conclusions/Significance: SPOKE enables the integration of seemingly disparate information to support precision medicine efforts. AVAILABILITY AND IMPLEMENTATION: The SPOKE neighborhood explorer is available at https://spoke.rbvi.ucsf.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Microbial dysbiosis in oral squamous cell carcinoma: A systematic review and meta-analysis.

Objective: The aim of this study was to summarize previously published data and assess the alterations in the composition of the oral microbiome in OSCC using a systematic review and meta-analysis. Design: Electronic databases were systematically searched for studies on the oral microbiome in OSCC published before December 2021. Qualitative assessments of compositional variations at the phylum level were performed. The meta-analysis on abundance changes of bacteria genera was performed via a random-effects model. Results: A total of 18 studies involving 1056 participants were included. They consisted of two categories of studies: 1) case-control studies (n = 9); 2) nine studies that compared the oral microbiome between cancerous tissues and paired paracancerous tissues. At the phylum level, enrichment of Fusobacteria but depletion in Actinobacteria and Firmicutes in the oral microbiome was demonstrated in both categories of studies. At the genus level, Fusobacterium showed an increased abundance in OSCC patients (SMD = 0.65, 95% CI: 0.43-0.87, Z = 5.809, P = 0.000) and in cancerous tissues (SMD = 0.54, 95% CI: 0.36-0.72, Z = 5.785, P = 0.000). The abundance of Streptococcus was decreased in OSCC (SMD = -0.46, 95% CI: -0.88-0.04, Z = -2.146, P = 0.032) and in cancerous tissues (SMD = -0.45, 95% CI: -0.78-0.13, Z = -2.726, P = 0.006). Conclusions: Disturbances in the interactions between enriched Fusobacterium and depleted Streptococcus may participate in or prompt the occurrence and development of OSCC and could be potential biomarkers for detection of OSCC.

Cognitive impairment is associated with sarcopenia mainly related to attention and calculation in hospitalized Chinese elderly men.

BACKGROUND AND OBJECTIVES: Sarcopenia and cognitive impairment are the most prevalent causes of disability in older individuals. The aim of this study was to assess the prevalence of sarcopenia and the association between cognitive impairment and sarcopenia in older patients. METHODS AND STUDY DESIGN: A cross-sectional study was undertaken, comprised 250 male patients aged 65 and over. Sarcopenia was defined using the diagnostic recommended consensus by the Asian Working Group for sarcopenia, and the participants were classified into the sarcopenia and non-sarcopenia groups according to this definition. The cognitive functions of older patients were assessed using the Mini-Mental State Examination (MMSE). After bivariate analyses, a multivariate logistic regression model was constructed to determine the association of study variables with sarcopenia. RESULTS: The prevalence of sarcopenia and cognitive impairment was 20.8% and 19.6% respectively. Additionally, we found 10.8% patients had nutritional risk, 19.6% patients had cognitive impairment in this study. Multivariate analysis identified age (OR: 1.11, 95% Cl 1.03, 1.19, p=0.008), cognitive impairment (OR: 4.06, 95% Cl 1.42, 11.6, p=0.009) and nutritional risk (OR: 13.7, 95% Cl 3.06, 61.2, p=0.001) were significantly associated with sarcopenia. The prevalence of sarcopenia significantly increased stepwise with lower MMSE score. Additionally, the score on the attention and calculation (OR=0.68, 95% Cl: 0.51, 0.91, p=0.009) subsection of the MMSE was associated with the presence of sarcopenia. MMSE score was correlated with the fat free mass, handgrip strength (p<0.05). CONCLUSIONS: Cognitive impairment, especially in the calculation and attention, and nutritional risk, are associated with sarcopenia in hospitalized Chinese male elderly. Adequate nutritional support may be the key to solving these diseases.

Effects of pre-operative enteral immunonutrition for esophageal cancer patients treated with neoadjuvant chemoradiotherapy: protocol for a multicenter randomized controlled trial (point trial, pre-operative immunonutrition therapy).

BACKGROUND: Neoadjuvant chemoradiation followed by esophagectomy has been established as the first-line treatment for locally advanced esophageal cancer. Postoperative enteral nutrition has been widely used to improve perioperative outcomes. However, whether to implement preoperative nutritional intervention during neoadjuvant therapy is yet to be verified by prospective studies. METHODS: POINT trial is a multicenter, open-labeled, randomized controlled trial. A total of 244 patients with surgically resectable esophageal cancer are randomly assigned to nutritional therapy group (arm A) or control group (arm B) with a 2:1 ratio. Both groups receive neoadjuvant chemotherapy with concurrent radiotherapy based on the CROSS regimen followed by minimally invasive esophagectomy. The primary endpoint is the rate of nutrition and immune-related complications after surgery. Secondary endpoints include completion rate of neoadjuvant chemoradiation and related adverse events, rate of pathological complete response, perioperative outcomes, nutritional status, overall survival, progression-free survival and quality of life. DISCUSSION: This trial aims to verify whether immunonutrition during neoadjuvant chemoradiation can reduce the rate of complications and improve perioperative outcomes. Frequent communication and monitoring are essential for a multicenter investigator-initiated trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04513418. The trial was prospectively registered on 14 August 2020, https://www. CLINICALTRIALS: gov/ct2/show/NCT04513418 .

A Panel of E2F Target Gene Signature Predicting the Prognosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma is one of the most malignant tumors, and the therapeutic effects of traditional treatments are poor. It is urgent to explore and identify new biomarkers and therapeutic targets to develop novel treatments which are individualized and effective. Three hallmarks, including E2F targets, G2M checkpoint and DNA repair, were collected by GSEA analysis. The panel of E2F-related gene signature consisted of five genes: HN1, KIF4A, CDCA3, CDCA8 and SSRP1. They had various mutation rates ranging from 0.8 to 5% in hepatocellular carcinoma, and patients with gene mutation had poorer prognosis. Among these genes, HN1 has the greatest mutation rate, and SSRP1 has the greatest impact on the model with a B (COX) value of 0.8842. Patients with higher expression of these genes had poorer prognosis. Kaplan-Meier curves in stratified survival analysis confirmed that patients with high risk scores had poor prognosis (p < 0.05). The results of univariate and multivariate COX survival analysis showed that risk score was closely related to the overall survival of patients with hepatocellular carcinoma. For clinical validation, we found that all the genes in the model were upregulated in hepatocellular carcinoma tissues compared to normal liver tissues, which was consistent with the previous results we obtained. Our study demonstrated that a panel of E2F target genes signature including five genes could predict the prognosis of hepatocellular carcinoma. This panel gene signature can facilitate the development of individualized and effective treatment for hepatocellular carcinoma.

The methylation modification of m6A regulators contributes to the prognosis of ovarian cancer.

Background: Ovarian cancer (OV) is the leading cause of death in gynecological cancer. The dysregulation of N6-methyladenosine (m6A) modification is commonly found in cancers. However, there is a lack of research into m6A RNA methylation regulators in OV. Methods: The RNA-Seq of 379 OV tissues and 88 healthy ovarian tissues was downloaded from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, respectively. A Gene Ontology (GO) functional analysis was performed to verify the function of m6A RNA methylation regulators. Kaplan-Meier (K-M) curves and the log-rank (Mantel-Cox) test were used for the survival analysis. A Cox regression analysis was used to identify the genes related to overall survival (OS) and build the prediction model. Results: m6A RNA methylation regulators were dysregulated in OV tissues compared with normal tissues (P<0.05), and patients with a high expression of KIAA1429 and YTHDC2 had a poor prognosis (P<0.05). A prognostic model was constructed based on the m6A RNA methylation regulators. Based on the risk signature, the patients were classified into high- and low-risk groups. The low-risk group's OS rate was significantly better than that of the high-risk group. The validity and accuracy of the prognostic model were verified by using TCGA and Gene Expression Omnibus (GEO) datasets, and the risk score from the prognostic model acted as an independent prognostic indicator in predicting the survival of OV patients. Conclusions: m6A RNA methylation regulators were dysregulated in OV tissues. More importantly, the prognostic model comprising the five selected m6A RNA methylation regulators could be a valuable tool for predicting the prognosis of OV patients.

Association between Dietary Inflammatory Index and Sarcopenia in Crohn's Disease Patients.

BACKGROUND: Chronic inflammation is a pathophysiological cause of sarcopenia in Crohn's disease (CD) patients. However, the potential impact of diet-related inflammation on sarcopenia has not yet been adequately investigated. We examined the associations between Dietary Inflammatory Index (DII) and sarcopenia in CD patients. METHODS: A total of 140 CD patients from Ruijin Hospital in Shanghai were included in this cross-sectional study. DII scores were calculated from the dietary data collected using a validated food frequency questionnaire (FFQ). Sarcopenia was determined according to the Asian Working Group for Sarcopenia. Multivariable logistic regression analyses were performed to determine the association between DII and sarcopenia. RESULTS: The mean DII score was 0.81 ± 2.13, ranging from -3.24 to 4.89. The overall prevalence of sarcopenia was 26.4%. The higher DII score significantly increased the risk of sarcopenia in CD patients (ORQuartile4vs1: 9.59, 95% CI: 1.69, 54.42, ptrend = 0.031) in the multivariable model after adjusting for more potential confounders. Moreover, CD patients with a lower DII had a significantly higher appendicular skeletal muscle mass index (ASMI, ORQuartile4vs1: 5.48, 95% CI: 1.51, 19.87, ptrend = 0.018) after adjusting for age, gender, BMI, smoking status and drinking status model. Yet, there were no significant differences between DII and ASMI after adjusting for more potential confounders. Additionally, no significant association was observed between DII and handgrip strength in the multivariable-adjusted models. CONCLUSIONS: Pro-inflammatory diet was associated with increased risk of sarcopenia in CD patients. CD patients should have a proper intake of energy and protein. These patients could also benefit from supplementation with enteral nutrition due to its anti-inflammatory potential.

Role of perioperative nutritional status and enteral nutrition in predicting and preventing post-operative complications in patients with Crohn's disease.

Background: Perioperative immune-nutritional status is correlated with post-operative outcomes. This study aimed to evaluate whether pre-operative nutritional status could predict post-operative complications in patients with Crohn's disease (CD) and whether pre-operative enteral nutrition (EN) can prevent post-operative complications. Methods: This retrospective cohort study analyzed the electronic health records of 173 patients diagnosed with CD in Ruijin Hospital, Shanghai, China, between August 2015 and May 2021: 122 patients had pre-operative nutritional support while 51 patients underwent surgery without pre-operative nutritional support. The pre-operative nutritional status, disease activity index, disease-related data, frequency of multiple surgery, operative data, and post-operative characters in each group were compared to determine whether the nutritional support and status could significantly affect post-operative outcome. One-to-one propensity score matching (PSM) was performed to limit demographic inequalities between the two groups. Results: After PSM, no statistically significant differences were found in pre-operative patient basic characteristics between the two groups of 47 patients (98 patients in all) included in this study. Overall, 21 patients developed 26 post-operative complications. In terms of pre-operative nutritional status, the level of serum albumin (ALB), pre-albumin (pre-ALB), and hemoglobin (Hb) in the nutrition group were statistically higher than that in the control group. We also observed a statistically significant decrease in post-operative complications, need for emergency surgery, and staged operations, while the rate of laparoscopic surgery was higher in the nutrition group compared to the non-nutritional group. Post-operative complications were related to pre-operative nutritional condition, which indicated that EN may improve the nutritional status and reduced the rate of post-operative complications. Conclusion: Pre-operative nutritional status is correlated with post-operative outcomes while EN plays a positive role in preventing the post-operative complications. EN is useful for improving the pre-operative nutritional status and reducing the post-operative adverse events for CD patients undergoing surgery.

The Influencing Factors of Nutrition and Diet Health Knowledge Dissemination Using the WeChat Official Account in Health Promotion.

Background: The promotion of a healthy diet via health education is a component of the "Healthy China 2030" plan. However, few studies have reported whether health knowledge about nutrition and diet has gained public attention, and whether it is needed by the public. Methods: The numbers of views, shares, and reads of articles published by the official WeChat account of a hospital in China were accessed. The influence index was obtained via the entropy analysis of these three indices. A questionnaire survey was developed based on the purpose of the study and the conclusion of the content analysis, which conducted to analyze users' requirements for health knowledge and their influencing factors. Moreover, risk factors were explored by logistic regression models. Results: Of the 103 articles considered in this study, four articles in the Top 10 were related to nutrition and diet. The influence index of nutrition and diet knowledge was found to be the highest in the content analysis (p < 0.05). The higher degrees of humor (ß = 0.224, p = 0.027), nutrition and diet articles (ß = 0.776, p = 0.034), and cover articles (ß = 0.312, p = 0.021) have significant influences on the influence index. In total, 581 questionnaires were obtained, and 78.1% of the respondents reported believing that the health knowledge of greatest concern was that related to nutrition and diet. Multivariate logistic regression analyses were conducted to explore the associations between the features of the articles and users reading nutrition and diet knowledge; it was found that gender (female, OR: 4.651, 95%Cl: 2.598, 8.325, and p < 0.001), age (young adult, OR: 0.358, 95%Cl: 0.266, 0.481, and p < 0.001), cancer precaution knowledge (OR: 4.333, 95%Cl: 2.262, 8.299, and p < 0.001), traditional Chinese medicine (OR: 2.121, 95%Cl: 1.064, 4.230, and p = 0.033), the knowledge acquisition approach [circle of friends (OR: 2.586, 95%Cl: 1.373, 4.868, and p = 0.003), social media (OR: 2.183, 95%Cl: 1.204, 3.960, and p = 0.010)), hospitals (OR: 3.194, 95%Cl: 1.793, 5.692, and p < 0.001), television media (OR: 4.348, 95%Cl: 2.341, 8.077, and p < 0.001)], and social media strategies [professionalism and authority (OR: 2.354, 95%Cl: 1.231, 4.505, and p = 0.006)] have statistically significant relationships with users reading nutrition and diet knowledge. Conclusion: Nutrition and diet knowledge could contribute to WeChat user engagement of health information dissemination. Nutrition professionals should improve the scientific popularization ability and effectively use social media for health promotion.

Body Mass Index and Disease Activity Are Associated With Moderate to Severe Disability in Crohn's Disease: A Cross-Sectional Study in Shanghai.

Background: The inflammatory bowel disease disability index (IBD-DI) was used to access body functional consequences and disease burden. However, Chinese population data are considerably limited. Objective: We aimed to screen for disability in patients with Crohn's disease (CD) and to assess potential associations with clinical parameters as well as indices related to sarcopenia. Methods: This cross-sectional study includes 146 CD patients from Ruijin Hospital in Shanghai, China. All patients were screened for disability and sarcopenia on the basis of the IBD-DI scale, and the criteria for Asian Working Group for Sarcopenia, respectively. Clinical and demographic variables were collected. Results: Approximately 52.05% of the subjects suffered from moderate or severe disabilities. The prevalence of sarcopenia (48.68 vs. 31.43%, P = 0.043), Patient-Generated Subjective Global Assessment score or PG-SGA≥4 (39.47 vs. 17.14%, P = 0.003), and high-level C- reactive protein (27.63 vs. 11.43%, P = 0.021) were higher in patients with moderate to severe disability than in those without to minimal disability. By multivariate regression modeling, the following were identified as independent factors related to moderate to severe disability: disease activity (OR:10.47, 95% CI: 2.09-52.42) and body mass index (BMI) (OR:4.11, 95% CI: 1.80-9.38). Conclusions: Disability is common in CD patients. Our study showed that moderate to severe disability is not directly associated with muscle mass or muscle quantity but is mostly correlated with disease activity as well as BMI. Thus, close monitoring and follow-up should be conducted on patients who are at high risk of disability, and effective measures should be taken, which may be the best way to prevent disability.

Therapeutic effect of ursolic acid on fetal development in pregnant rats with gestational diabetes mellitus via AGEs-RAGE signaling pathway.

To investigate the effect of ursolic acid on the fetal development of gestational diabetes mellitus (GDM) caused by streptozotocin (STZ) and explore the potential mechanism for it. For the current experimental research, SD rats (pregnant animal) were used. STZ has been used to cause the diabetes mellitus in pregnant rats. Rats with evolved GDM were randomly divided and ursolic acid was given to pregnant rats in the experimental period up to 19 days in a dose-dependent manner. Blood samples and fetal rats of all group rats were collected at 19 days (pregnant rats), fetal rats and placental rats were weighted and the blood glucose, plasma insulin, C-peptide, and lipid parameters of pregnant women were estimated prior to delivery. Advanced serum glycation end-products (AGEs) were estimated at regular intervals in the heart and brain of pregnant rats. Monocyte Chemoattractant Protein-1 (MCP-1), NADPH oxidase 2 (Nox2), Role of advanced glycation end product (RAGE), Vascular endothelial growth factor (VEGF), p65, and vascular cell adhesion molecule 1 (VCAM-1) mRNA expression were estimated in the placenta. STZ-induced GDM pregnant rats showed significantly decreased placental weight and weight of fetal rats and dose-dependent ursolic acid treatment (p < .001) improved placental weight and weight of fetal rats at dose-dependent levels. After the ursolic acid treatment, serum blood glucose and lipid level were improved especially fasting blood glucose (FBG), high density lipoprotein (HDL), hepatic glycogen, fasting insulin (FINS), and serum insulin level and reached near to the normal control group rats. The antioxidant level of pancreas and liver were significantly (p < .001) reduced by the dose-dependent treatment of ursolic acid. Treatment with Ursolic acid moderately but not significantly decreases the risk of fetal development defects relative to the GDM group. The potential effect on fetal development in Pregnant Rats with Gestational Diabetes Mellitus via AGEs-RAGE signaling pathway was shown by Ursolic acid. PRACTICAL APPLICATIONS: As we know that the gestational diabetes mellitus increases worldwide day by day. In the current experimental study, we try to examine the gestational diabetic effect of ursolic acid. The finding of the current study showed the gestational diabetic protective effect in the female rats via AGEs-RAGE signaling pathway. The result showed the antioxidant, anti-inflammatory, and biochemical parameters. On the basis of the result, we can say that the ursolic acid can be the protective drug for treatment of gestational diabetes mellitus.

Nutritional assessment and risk factors associated to malnutrition in patients with esophageal cancer.

INTRODUCTION: Esophageal cancer is the fourth most common cause of cancer death in China. Patients with esophageal cancer are more likely to suffer from malnutrition. The purpose of this study is to assess nutritional status of patients with esophageal cancer from multiple perspectives and analyze the risk factors. METHODS: A total of 1482 esophageal cancer patients were enrolled in the study. We investigated the Scored Patient Generated Subjective Global Assessment (PG-SGA) scores, NRS-2002 scores, Karnofsky performance status scores, anthropometric, and laboratory indicators of patients. Unconditional logistic regression analysis was applied to identify the risk factors of nutritional status. RESULTS: PG-SGA (≥4) and NRS-2002 (≥3) showed the incidence of malnutrition were 76% and 50%, respectively. In the patients with PG-SGA score ≥4, the proportion of patients who did not receive any nutritional support was 60%. The incidence of malnutrition in females was significantly higher than that in males. Besides, abnormality rates of Red blood cell (P < 0.001), MAC (P = 0.037), and MAMC (P < 0.001) in males was significantly higher than that in females, while abnormality rates of TSF (P < 0.001) was lower than that in females. After adjusted with the other potential risk factors listed, unconditional logistic regression analysis indicated smoking (odds ratio: 2.868, 95% confidence interval: 1.660-4.954), drinking (OR: 1.726, 95% CI: 1.099-2.712), family history (OR: 1.840, 95% CI: 1.132-2.992), radiotherapy or chemotherapy (OR: 1.594, 95% CI: 1.065-2.387), and pathological stage (OR: 2.263, 95% CI: 1.084-4.726) might be the risk factors of nutritional status, while nutritional support can reduce the risk of malnutrition. CONCLUSION: Effective nutritional risk assessment methods and nutritional intervention measures can be adopted according to the research data to improve quality of life of esophageal cancer patients.

The Effect of Hedysarum multijugum Maxim.-Chuanxiong rhizoma Compound on Ischemic Stroke: A Research Based on Network and Experimental Pharmacology.

BACKGROUND: Hedysarum multijugum Maxim.-Chuanxiong rhizoma compound (HCC) is a common herbal formula modified from Buyang Huanwu decoction. Clinical trials have demonstrated its therapeutic potential for ischemic stroke (IS). However, the mechanism of HCC remains unclear. METHODS: The HCC's components were collected from the TCMSP database and TCM@Taiwan database. After that, the HCC's compound targets were predicted by PharmMapper. The IS-related genes were obtained from GeneCards, and OMIM and the protein-protein interaction (PPI) data of HCC's targets and IS genes were obtained from the String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis and the Cytoscape 3.7.2 was utilized to construct and analyze the networks. Finally, a series of animal experiments were carried out to validate the prediction results of network pharmacology. The expressions of GRP78, p-PERK, and CHOP proteins and mRNAs in different time periods after HCC intervention were detected by Western blot, immunohistochemistry, and RT-qPCR. RESULTS: A total of 440 potential targets and 388 IS genes were obtained. The results of HCC-IS PPI network analysis showed that HCC may regulate IS-related targets (such as ALB, AKT1, MMP9, IGF1, and CASP3), biological processes (such as endoplasmic reticulum stress, inflammation modules, hypoxia modules, regulation of neuronal apoptosis and proliferation, and angiogenesis), and signaling pathways (such as PI3K-Akt, FoxO, TNF, HIF-1, and Rap1 signaling). The animal experiments showed that HCC can improve the neurobehavioral scores and protect the neurons of IS rats (P < 0.05). HCC inhibited the expression of p-PERK in the PERK pathway from 12 h after surgery, significantly promoted the expression of GRP78 protein, and inhibited the expression of CHOP protein after surgery, especially at 24 h after surgery (P < 0.05). The results of RT-qPCR showed that HCC can significantly reduce the expression of CHOP mRNA in the neurons in the CA1 region of the hippocampus 72 h after MCAO (P < 0.05). CONCLUSION: HCC may achieve a role in the treatment of IS by intervening in a series of targets, signaling pathways, and biological processes such as inflammation, oxidative stress, endoplasmic reticulum stress, and angiogenesis.

Nutritional status and survival of 8247 cancer patients with or without diabetes mellitus-results from a prospective cohort study.

BACKGROUND: The number of cancer patients with diabetes mellitus (DM) is steadily rising. Little is known about the nutritional status of this population. This study characterized the nutritional status and survival of cancer patients with diabetes compared with those without diabetes. METHODS: A total of 8247 cancer patients were prospectively enrolled from 72 hospitals in China and followed until August 2019. A global estimation of the nutritional status was performed for each participant using standardized tools. The outcomes were cancer-specific survival (CSS) and overall survival (OS). RESULTS: The incidence of diabetes was 7.6% in the whole population. In comparison with the non-DM group, the DM group had greater body weight, but a similar fat-free mass, a lower handgrip strength and a decreased Karnofsky performance score. A higher proportion of patients with diabetes were overweight/obese as indicated by BMI. The percentage of patients who were at risk of malnutrition (evaluated by PG-SGA) was higher in the DM group (score ≥ 4, 56.7% vs 52.9%). Patients with DM showed a worse CSS (4-year CSS, 62% vs 73%) and OS (4-year OS 39% vs 52%). Diabetes was associated with an increased risk of both cancer-specific (hazard ratio (HR) = 1.282, 95% confidence interval (CI) 1.070-1.536) and overall (HR = 1.206, 95% CI 1.040-1.399) mortality. CONCLUSIONS: Cancer patients with diabetes had a larger body mass but lower muscle strength, poorer performance status and higher incidence of malnourishment. Diabetes was associated with compromised survival. Tailored nutritional intervention is necessary for this subpopulation of patients.

Predicting conversion to Alzheimer's disease among individual high-risk patients using the Characterizing AD Risk Events index model.

AIMS: Both amnestic mild cognitive impairment (aMCI) and remitted late-onset depression (rLOD) confer a high risk of developing Alzheimer's disease (AD). This study aims to determine whether the Characterizing AD Risk Events (CARE) index model can effectively predict conversion in individuals at high risk for AD development either in an independent aMCI population or in an rLOD population. METHODS: The CARE index model was constructed based on the event-based probabilistic framework fusion of AD biomarkers to differentiate individuals progressing to AD from cognitively stable individuals in the aMCI population (27 stable subjects, 6 progressive subjects) and rLOD population (29 stable subjects, 10 progressive subjects) during the follow-up period. RESULTS: AD diagnoses were predicted in the aMCI population with a balanced accuracy of 80.6%, a sensitivity of 83.3%, and a specificity of 77.8%. They were also predicted in the rLOD population with a balanced accuracy of 74.5%, a sensitivity of 80.0%, and a specificity of 69.0%. In addition, the CARE index scores were observed to be negatively correlated with the composite Z scores for episodic memory (R2  = .17, P < .001) at baseline in the combined high-risk population (N = 72). CONCLUSIONS: The CARE index model can be used for the prediction of conversion to AD in both aMCI and rLOD populations effectively. Additionally, it can be used to monitor the disease severity of patients.

Genetic Variants of PICALM rs541458 Modulate Brain Spontaneous Activity in Older Adults With Amnestic Mild Cognitive Impairment.

Background: Phosphatidylinositol binding clathrin assembly protein (PICALM) rs541458 C allele has been identified and validated to be associated with a reduction of Alzheimer's disease (AD) risk. Nevertheless, the exact mechanisms through which the variant exert its disease-relevant association remain to be elucidated. This study is to determine whether PICALM rs541458 polymorphism modulates functional magnetic resonance imaging measured brain spontaneous activity in older adults with amnestic mild cognitive impairment (aMCI). Methods: Thirty five aMCI patients and twenty six healthy controls (HC) were enrolled in this study. Each individual was genotyped for rs541458 and scanned with resting-state functional magnetic resonance imaging. Each group was divided into two subgroups (C carriers and TT genotype). Brain activity was measured with amplitude of low-frequency fluctuation (ALFF). Results: The aMCI patients showed decreased ALFF in left inferior frontal gyrus, superior temporal gyrus and insula, while increased ALFF in right cuneus, calcarine, and bilateral posterior cingulate and precuneus. A significant interaction between diagnosis (aMCI vs. HC) and PICALM rs541458 genotype (C carriers vs. TT) on ALFF was observed mainly in the right frontal lobe, with aMCI C carriers and TT genotype in HC showing significantly lower ALFF than HC C carriers. While only negative correlation between ALFF and verbal fluency test was found in HC C carriers (r = -0.543, p = 0.030). Conclusions: This study provided preliminary evidences that PICALM rs541458 variations may modulate the spontaneous brain activity in aMCI patients.

Distinct neural correlates of episodic memory among apolipoprotein E alleles in cognitively normal elderly.

The apolipoprotein E (APOE) ε4 and ε2 alleles are acknowledged genetic factors modulating Alzheimer's disease (AD) risk and episodic memory (EM) deterioration in an opposite manner. Mounting neuroimaging studies describe EM-related brain activity differences among APOE alleles but remain limited in elucidating the underlying mechanism. Here, we hypothesized that the APOE ε2, ε3, and ε4 alleles have distinct EM neural substrates, as a manifestation of degeneracy, underlying their modulations on EM-related brain activity and AD susceptibility. To test the hypothesis, we identified neural correlates of EM function by correlating intrinsic hippocampal functional connectivity networks with neuropsychological EM performances in a voxelwise manner, with 129 cognitively normal elderly subjects (36 ε2 carriers, 44 ε3 homozygotes, and 49 ε4 carriers). We demonstrated significantly different EM neural correlates among the three APOE allele groups. Specifically, in the ε3 homozygotes, positive EM neural correlates were characterized in the Papez circuit regions; in the ε4 carriers, positive EM neural correlates involved the lateral temporal cortex, premotor cortex/sensorimotor cortex/superior parietal lobule, and cuneus; and in the ε2 carriers, negative EM neural correlates appeared in the bilateral frontopolar, posteromedial, and sensorimotor cortex. Further, in the ε4 carriers, the interaction between age and EM function occurred in the temporoparietal junction and prefrontal cortex. Our findings suggest that the underlying mechanism of APOE polymorphism modulations on EM function and AD susceptibility is genetically related to the neural degeneracy of EM function across APOE alleles.