Blastocyst-like structures generated from human pluripotent stem cells.

Limited access to embryos has hampered the study of human embryogenesis and disorders that occur during early pregnancy. Human pluripotent stem cells provide an alternative means to study human development in a dish1-7. Recent advances in partial embryo models derived from human pluripotent stem cells have enabled human development to be examined at early post-implantation stages8-14. However, models of the pre-implantation human blastocyst are lacking. Starting from naive human pluripotent stem cells, here we developed an effective three-dimensional culture strategy with successive lineage differentiation and self-organization to generate blastocyst-like structures in vitro. These structures-which we term 'human blastoids'-resemble human blastocysts in terms of their morphology, size, cell number, and composition and allocation of different cell lineages. Single-cell RNA-sequencing analyses also reveal the transcriptomic similarity of blastoids to blastocysts. Human blastoids are amenable to embryonic and extra-embryonic stem cell derivation and can further develop into peri-implantation embryo-like structures in vitro. Using chemical perturbations, we show that specific isozymes of protein kinase C have a critical function in the formation of the blastoid cavity. Human blastoids provide a readily accessible, scalable, versatile and perturbable alternative to blastocysts for studying early human development, understanding early pregnancy loss and gaining insights into early developmental defects.

Biomimetic Mineralization Synthesis of Flower-Like Cobalt Selenide/Reduced Graphene Oxide for Improved Electrochemical Deionization.

Rationally and precisely tuning the composition and structure of materials is a viable strategy to improve electrochemical deionization (EDI) performances, which yet faces enormous challenges. Herein, an eco-friendly biomimetic mineralization synthetic strategy is developed to synthesize the flower-like cobalt selenide/reduced graphene oxide (Bio-CoSe2 /rGO) composites and used as advanced sodium ion adsorption electrodes. Benefiting from the slow and controllable reaction kinetics provided by the biomimetic mineralization process, the flower-like CoSe2 is uniformly constructed in the rGO, which is endowed with robust architecture, substantial adsorption sites and rapid charge/ion transport. The Bio-CoSe2 /rGO electrode yields the maximum salt adsorption capacity and salt adsorption rate of 56.3 mg g-1 and 5.6 mg g-1 min-1 respectively, and 92.5% capacity retention after 60 cycles. These results overmatch the pristine CoSe2 and irregular granular CoSe2 /rGO synthesized by a hydrothermal method, proving the structural superiority of the Bio-CoSe2 /rGO composites. Furthermore, the in-depth adsorption kinetics study indicates the chemisorption nature of sodium ion adsorption. The structures of the Bio-CoSe2 /rGO composites after long term EDI cycles are intensively studied to unveil the mechanism behind such superior EDI performances. This study offers one effective method for constructing advanced EDI electrodes, and enriches the application of the biomimetic mineralization synthetic strategy.

Therapeutic effect of implanted and non-invasive vagus nerve stimulation on heroin-induced anxiety.

Substance addiction causes anxiety, which in turn reinforces the maintaining of substance use, resulting in a vicious circle. And this circle is one of the reasons why addiction is so hard to cure. However, there is no treatment involved in addiction-induced anxiety at present. We tested whether VNS (vagus nerve stimulation) can improve heroin-induced anxiety, and made a comparison between nVNS (transcervical vagus nerve stimulation) and taVNS (transauricular vagus nerve stimulation) on therapeutic effect. Mice were subjected to nVNS or taVNS before heroin administration. By observing c-Fos expression in the NTS (nucleus of the solitary tract), we assessed vagal fiber activation. Using the OFT (open field test) and the EPM (elevated cross maze test), we evaluated the anxiety-like behaviors of the mice. Using immunofluorescence, we observed the proliferation and activation of microglia in the hippocampus. And ELISA was used to measure the levels of proinflammatory factors in the hippocampus. Both nVNS and taVNS significantly increased the expression of c-Fos in the nucleus of solitary tract, suggesting the feasibility of nVNS and taVNS. The anxiety level of heroin-treated mice was significantly increased, microglia in the hippocampus was significantly proliferated and activated, and the proinflammatory factors (IL-1ß, IL-6, TNF-α) in the hippocampus were significantly up-regulated. Crucially, both nVNS and taVNS reversed the above changes caused by heroin addiction. SIGNIFICANCE: It was confirmed that the therapeutic effect of VNS on heroin-induced anxiety may be an effective treatment method to break the "addiction-anxiety" cycle and provides some insights for subsequent treatment of addiction.

The role of germanium in diseases: exploring its important biological effects.

With the development of organic germanium and nanotechnology, germanium serves multiple biological functions, and its potential value in biochemistry and medicine has increasingly captured the attention of researchers. In recent years, germanium has gradually gained significance as a material in the field of biomedicine and shows promising application prospects. However, there has been a limited amount of research conducted on the biological effects and mechanisms of germanium, and a systematic evaluation is still lacking. Therefore, the aim of this review is to systematically examine the application of germanium in the field of biomedicine and contribute new insights for future research on the functions and mechanisms of germanium in disease treatment. By conducting a comprehensive search on MEDLINE, EMBASE, and Web of Science databases, we systematically reviewed the relevant literature on the relationship between germanium and biomedicine. In this review, we will describe the biological activities of germanium in inflammation, immunity, and antioxidation. Furthermore, we will discuss its role in the treatment of neuroscience and oncology-related conditions. This comprehensive exploration of germanium provides a valuable foundation for the future application of this element in disease intervention, diagnosis, and prevention.

Association of Phase Angle with Overall Survival in Patients with Cancer: A Prospective Multicenter Cohort Study.

Low phase angle (PhA) is related with poor clinical status of cancer patients. The objective of this study was to establish sex- and age-specific cutoff points and examine the association between PhA and overall survival (OS) in Chinese cancer patients. This cohort study included data on 1,814 patients with cancer from December 2013 to October 2020. The association between low PhA and overall survival was analyzed using the Kaplan-Meier method and Cox regression model. Among 1,814 participants, there were 993 (54.70%) male and 821 (45.30%) female patients. The optimal cutoff points of low PhA were 4.8°, 4.2°, 4.4°, and 3.8° for the young male, elderly male, young female, and elderly female, respectively. Low PhA was independently associated with poorer OS in young female, elderly female and male (HR: 1.59, 95% CI: 1.08-2.34; HR: 1.65, 95% CI: 1.03-2.67; HR: 2.00, 95% CI: 1.45-2.75). In addition, low PhA was demonstrated to be an adverse prognostic factor in patients with lung cancer, colorectal cancer, and esophagus cancer (HR: 1.85, 95% CI: 1.39-2.47; HR: 2.05, 95% CI: 1.13-3.70; HR: 2.92, 95% CI: 1.49-5.71). Based on cutoff points, low PhA was associated with worse prognosis in patients with cancer.

Incremental diagnostic value of radiomics signature of pericoronary adipose tissue for detecting functional myocardial ischemia: a multicenter study.

OBJECTIVES: To determine the incremental diagnostic value of radiomics signature of pericoronary adipose tissue (PCAT) in addition to the coronary artery stenosis and plaque characters for detecting hemodynamic significant coronary artery disease (CAD) based on coronary computed tomography angiography (CCTA). METHODS: In a multicenter trial of 262 patients, CCTA and invasive coronary angiography were performed, with fractional flow reserve (FFR) in 306 vessels. A total of 13 conventional quantitative characteristics including plaque characteristics (N = 10) and epicardial adipose tissue characteristics (N = 3) were obtained. A total of 106 radiomics features depicting the phenotype of the PCAT surrounding the lesion were calculated. All data were randomly split into a training dataset (75%) and a testing dataset (25%). Then three models (including the conventional model, the PCAT radiomics model, and the combined model) were established in the training dataset using multivariate logistic regression algorithm based on the conventional quantitative features and the PCAT radiomics features after dimension reduction. RESULTS: A total of 124/306 vessels showed functional ischemia (FFR ≤ 0.80). The radiomics model performed better in discriminating ischemia from non-ischemia than the conventional model in both training (area under the receiver operating characteristic (ROC) curve (AUC): 0.770 vs 0.732, p < 0.05) and testing datasets (AUC: 0.740 vs 0.696, p < 0.05). The combined model showed significantly better discrimination than the conventional model in both training (AUC: 0.810 vs 0.732, p < 0.05) and testing datasets (AUC: 0.809 vs 0.696, p < 0.05). CONCLUSIONS: The PCAT radiomics model showed good performance in predicting myocardial ischemia. Addition of PCAT radiomics to lesion quantitative characteristics improves the predictive power of functionally relevant CAD. KEY POINTS: • Based on the plaque characteristics and EAT characteristics, the conventional model showed poor performance in predicting myocardial ischemia. • The PCAT radiomics model showed good prospect in predicting myocardial ischemia. • When combining the radiomics signature with the conventional quantitative features (including plaque features and EAT features), it showed significantly better performance in predicting myocardial ischemia.

Population-Level Configurations of Gut Mycobiome Across 6 Ethnicities in Urban and Rural China.

BACKGROUND & AIMS: Beyond bacteria, the human gastrointestinal tract is host to a vast diversity of fungi, collectively known as the gut mycobiome. Little is known of the impact of geography, ethnicity, and urbanization on the gut mycobiome at a large population level. We aim to delineate the variation of human gut mycobiome and its association with host factors, environmental factors, and diets. METHODS: Using shotgun metagenomic sequencing, we profiled and compared the fecal mycobiome of 942 healthy individuals across different geographic regions in China (Hong Kong and Yunnan), spanning 6 ethnicities: Han, Zang, Bai, Hani, Dai, and Miao (including both urban and rural residents of each ethnicity). In parallel to fecal sampling, we collected participant metadata (environmental exposure, bowel habits, anthropometrics, and medication), diet, and clinical blood measurement results (a total of 118 variables) and investigated their impact on the gut mycobiome variation in humans. RESULTS: The human gut mycobiome was highly variable across populations. Urbanization-related factors had the strongest impact on gut mycobiome variation, followed by geography, dietary habit, and ethnicity. The Hong Kong population (highly urbanized) had a significantly lower fungal richness compared with Yunnan population. Saccharomyces cerevisiae was highly enriched in urban compared with rural populations and showed significant inverse correlations with liver pathology-associated blood parameters, including aspartate transaminase, alanine transaminase, gamma-glutamyltransferase, and direct bilirubin. Candida dubliniensis, which was decreased in urban relative to rural populations, showed correlations with host metabolism-related parameters in blood, including a positive correlation with fasting high-density lipoprotein cholesterol levels and a negative correlation with fasting glucose levels. The fungal-blood parameter correlations were highly geography- and ethnicity-specific. Food choices had differential influences on gut mycobiome and bacterial microbiome, where taxa from the same genus tended to be coregulated by food and thereby cobloom. Ethnicity-specific fungal signatures were associated with distinct habitual foods in each ethnic group. CONCLUSIONS: Our data highlight, for the first time to our knowledge, that geography, urbanization, ethnicity, and habitual diet play an important role in shaping the gut mycobiome composition. Gut fungal configurations in combination with population characteristics (such as residing region, ethnicity, diet, lifestyle) influence host metabolism and health.

Long-term exercise at different intensities can reduce the inflammatory response in the brains of methamphetamine-treated mice.

Methamphetamine (METH) is a highly addictive psychoactive drug that is used worldwide. Various approaches have been used to address METH dependence, but many of them have little effect. Previous studies have shown that exercise on a treadmill could reduce METH dependence in mice, but the intensity and duration of exercise that was needed to be effective was unknown. This study investigated the effects of low- and medium-intensity treadmill exercise on methamphetamine reward in male mice via conditioned place preference (CPP) training, and the levels of the inflammatory factors IL-1ß, IL-6 and TNF-α in three brain regions (cerebral cortex, hippocampus and striatum) were determined. The results showed that long-term medium-intensity exercise reduced the effects of methamphetamine on inflammation markers in the brain and CPP scores. In addition, long-term medium-intensity exercise decreased IL-1ß concentrations in the cerebral cortex and hippocampus, reduced IL-6 concentrations in the striatum, and reduced TNF-α concentrations in the cerebral cortex, hippocampus, and striatum in methamphetamine-treated mice; low-intensity exercise was less effective. The results indicated that long-term medium-intensity exercise could reduce concentrations of methamphetamine-induced encephalitis factors in male mice, while low-intensity exercise was less effective in alleviating dependence and inflammatory responses. It is suggested that exercise intensity is an important factor affecting the dependence level and inflammatory responses in the brain in mice administered methamphetamine.

Prognostic importance of systemic inflammation and insulin resistance in patients with cancer: a prospective multicenter study.

BACKGROUND: Systemic inflammation and insulin resistance (IR) are often associated with poor prognosis in cancer. This study aimed to investigate the prognostic value of surrogate systemic inflammation and IR indices in patients with cancer. METHODS: This multicenter prospective study included 5,221 patients with cancer, with a mean age of 59.41±11.15 years, of whom 3,061 (58.6%) were male. The surrogate IR indices included low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LHR) ratio, total cholesterol to high-density lipoprotein cholesterol (TC/ HDL-c) ratio, triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio, and fasting triglyceride glucose (TyG). Prognostic receiver operator characteristic (ROC) curves and C-indices were used to select a better surrogate IR index in patients with cancer. The prognostic value of the indicators was evaluated using univariate and multivariate survival analyses. RESULTS: In this study, the median survival time of patients was 44.5 (40.5-51.4) months, and the overall mortality in the 12-month period was 1,115 (53.7%), with 196 mortality events per 1,000 patient-years of patients' follow-up. The prognostic ROC curve and C-index suggested that the prognostic value of LHR was better than that of the other IR indices. The multivariate-adjusted hazard ratios (HRs) for overall survival (OS) were higher in patients with high C-reactive protein (CRP) (HR, 1.51; 95% confidence interval [CI]: 1.38-1.65) and high LHR (HR, 1.20; 95% CI: 1.06-1.37), respectively. The mortality rate of patients with both high CRP and LHR was 1.75-fold higher than that of patients with both low CRP and LHR. CONCLUSION: Both CRP and LHR showed good survival predictions in patients with cancer. CRP combined with LHR can improve the predictive power of patients with cancer.

The prognostic effect of hemoglobin on patients with cancer cachexia: a multicenter retrospective cohort study.

OBJECTIVES: To clarify the influence of hemoglobin on cancer cachexia and to determine whether hemoglobin affects the prognosis or quality of life of patients with cancer cachexia and whether these effects are caused by an interaction between hemoglobin and other factors. MATERIAL AND METHODS: This study was a multicenter cohort of 2715 patients with cancer cachexia diagnosed from June 2012 to December 2019. The primary outcomes and measures were overall survival (OS) time and all-cause mortality. The association between hemoglobin and all-cause mortality was evaluated using hazard ratios (HRs) and the restricted cubic spline model with a two-sided p-value. Optimal stratification was used to determine the threshold value. We also evaluated the cross-classification of hemoglobin and each variable with survival. RESULTS: Among the 2715 participants diagnosed with cancer cachexia, 1592 (58.6%) were male, and the mean (SD) age was 58.8 (11.7) years. The optimal cutoff point for hemoglobin as a predictor of cancer cachexia mortality was 140 g/L for males and 101 g/L for females in our research. The decrease in hemoglobin was positively correlated with all-cause mortality. These associations were consistent across cancer subtypes. In the multivariable analysis, after adjusting for sex, age, TNM stage, tumor type, radiotherapy, chemotherapy, Karnofsky performance status score, and other factors, patients diagnosed with cancer cachexia who had low hemoglobin levels were more likely to have a worse prognosis (HR 2.40; 95% CI, 1.12-1.51). CONCLUSION: Our results suggested that the proposed hemoglobin cutoff point would be valuable for prognostic prediction in patients with cancer cachexia, especially for long-term prognosis.

Efficacy of Global Leadership Initiative on Malnutrition as potential cachexia screening tool for patients with solid cancer.

PURPOSE: Cachexia has a very high prevalence in patients with cancer, and lacks effective screening tools yet. Global Leadership Initiative on Malnutrition (GLIM) is a novel malnutrition assessment tool, with increased important roles in malnutrition diagnosis for patients with cancer. However, whether GLIM can be used as an effective screening tool remains unknown. METHODS: We performed a multicenter cohort study including 8,478 solid tumor patients from 40 clinical centers throughout China. Cachexia was diagnosed based on the 2011 international cancer cachexia consensus. The receiver operating characteristic curves (ROC) and decision curve analysis (DCA) were developed to determine the efficacy and clinical net benefit of GLIM and Patient-Generated Subjective Global Assessment (PG-SGA) in the detection of cancer cachexia, respectively. RESULTS: According to the consensus guidelines, 1,441 (17.0%) cancer patients were diagnosed with cachexia among 8,478 patients in the present study. The sensitivity of one-step GLIM and two-step GLIM for detecting cachexia were 100 and 88.8%, respectively, while that of PG-SGA was 86.2%. The accuracies of one-step GLIM and two-step GLIM reached 67.4 and 91.3%, which were higher than that of PG-SGA (63.1%). The area under the curves (AUCs) of one-step GLIM (0.835) and two-step GLIM (0.910) were higher than PG-SGA (0.778) in patients with cancer. The DCA also revealed that two-step GLIM had better clinical effect than PG-SGA between 20-50% threshold probabilities. CONCLUSION: GLIM could be used as an effective tool in screening cancer cachexia, two-step GLIM criteria show more accurate while one-step GLIM criteria is more sensitive. TRIAL REGISTRATION: ChiCTR1800020329.

Comparison of Pain in Male Drug Rehabilitees with and without Human Immunodeficiency Virus in Yunnan Province, China.

BACKGROUND The purpose of this study was to compare pain symptoms in drug rehabilitees with or without human immunodeficiency virus (HIV) in Yunnan Province, China. MATERIAL AND METHODS This was a retrospective single-center cohort study. A total of 120 male substance users, including 65 with HIV, were enrolled after admission to the Fifth Drug Rehabilitation Center in Yunnan Province. Individuals who were >18 years of age and who had illicit drugs detected in their urine, despite not having used drugs for at least 2 months, were included. The patients evaluated their average pain intensity for the previous 4 weeks using a visual analog scale. PainDETECT questionnaire scores were used to classify pain into nociceptive and mixed component subgroups. Sleep quality was also evaluated using the Pittsburgh Sleep Quality Index scale. RESULTS The prevalence and intensity of the pain symptoms were higher for the drug rehabilitees with HIV than for those without HIV. Moreover, the rehabilitees with HIV were more likely to experience neuropathic and nociceptive pain, whereas those without HIV reported only nociceptive pain. The sleep quality of the rehabilitees with HIV was also lower, regardless of the pain symptoms. CONCLUSIONS Our results showed that the drug rehabilitees with HIV in Yunnan Province, China, experienced more frequent and stronger pain (both nociceptive and neuropathic) than those without HIV. They also experienced poorer sleep quality, although it was unrelated to pain. Our results provide data to support clinical diagnosis and treatment.

Iodine-125 induced cholangiocarcinoma cell death is enhanced by inhibition of endoplasmic reticulum stress-mediated protective autophagy.

Cholangiocarcinoma (CCA) is the second most common primary liver malignancy, however, it is difficult to diagnose and treat, and only a few patients with CCA are suitable for surgery. Iodine-125 (I-125) is an effective treatment for cancer, but the molecular mechanisms underlying the effects of I-125 differ among different cancers. This study aimed to explore the effects of I-125 on CCA cell activity and determine the possible mechanisms of action of I-125 in this type of cancer. CCA cell proliferation, cycling, apoptosis, autophagy, and endoplasmic reticulum (ER) stress were determined after irradiation of CCA cells with I-125 seeds. The effects of I-125 on autophagy and ER stress in three CCA cell lines were evaluated using western blotting, while the effects of I-125 on apoptosis and autophagy in QBC939 cells treated with si-Beclin1 or si-PERK, respectively, were assessed using flow cytometry. I-125 suppressed cell viability and induced cell cycle G2/M-phase arrest in three CCA cell lines (QBC939, TFK-1, HuCCT1). I-125 induced apoptosis, autophagy, and ER stress by altering the expression levels of some related proteins in each of the three CCA cell lines. Furthermore, autophagy inhibition (treatment with si-Beclin1) increased expression of apoptosis-related proteins (cleaved-PARP and cleaved-caspase-3, Bax/Bcl2) in QBC939 cells irradiated with I-125 seeds, while ER stress inhibition (with si-PERK) suppressed the expression of autophagy-related proteins (LC3-I, LC3-II, p62). Therefore, I-125 induces ER stress, thereby activating protective autophagy in CCA cells through the PERK signaling pathway. Combined inhibition of ER stress and autophagy signaling may increase the killing effect of I-125 on cancer cells and serve as a new auxiliary method in I-125 radiotherapy.

Ecological and network analyses identify four microbial species with potential significance for the diagnosis/treatment of ulcerative colitis (UC).

BACKGROUND: Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease (IBD), the occurrence of which has been increasing worldwide. Although IBD is an intensively studied human microbiome-associated disease, research on Chinese populations remains relatively limited, particularly on the mucosal microbiome. The present study aimed to analyze the changes in the mucosal microbiome associated with UC from the perspectives of medical ecology and complex network analysis. RESULTS: In total, 56 mucosal microbiome samples were collected from 28 Chinese UC patients and their healthy family partners, followed by amplicon sequencing. Based on sequencing data, we analyzed species diversity, shared species, and inter-species interactions at the whole community, main phyla, and core/periphery species levels. We identified four opportunistic "pathogens" (i.e., Clostridium tertium, Odoribacter splanchnicus, Ruminococcus gnavus, and Flavonifractor plautii) with potential significance for the diagnosis and treatment of UC, which were inhibited in healthy individuals, but unrestricted in the UC patients. In addition, we also discovered in this study: (i) The positive-to-negative links (P/N) ratio, which measures the balance of species interactions or inhibition effects in microbiome networks, was significantly higher in UC patients, indicating loss of inhibition against potentially opportunistic "pathogens" associated with dysbiosis. (ii) Previous studies have reported conflicting evidence regarding species diversity and composition between UC patients and healthy controls. Here, significant differences were found at the major phylum and core/periphery scales, but not at the whole community level. Thus, we argue that the paradoxical results found in existing studies are due to the scale effect. CONCLUSIONS: Our results reveal changes in the ecology and network structure of the gut mucosal microbiome that might be associated with UC, and these changes might provide potential therapeutic mechanisms of UC. The four opportunistic pathogens that were identified in the present study deserve further investigation in future studies.

Association between CD4+ T cell counts and gut microbiota and serum cytokines levels in HIV-infected immunological non-responders.

BACKGROUND: CD4+ T cell counts in certain human immunodeficiency virus (HIV)-infected patients called immunological non-responders (INRs) could not return to a normal level even with sustained antiretroviral therapy (ART) because of persistent immune activation, which is associated with pro-inflammatory cytokines production and an altered intestinal microbiome profile. Changes in gut bacterial composition have been linked to low CD4+ T cell counts in HIV-infected individuals. However, the association between CD4+ T cell counts and gut microbiota community composition and cytokines levels in INRs (CD4+ T cell counts < 500 cells/µL) from Yunnan Province, China, has not been previously investigated. METHODS: To address this issue, we carried out a cross-sectional study of 34 HIV-infected INRs. The patients were divided into CD4 count > 200 cells/µL group and CD4 count < 200 cells/µL group. The gut microbiota composition of each subject was analyzed by 16S rRNA gene sequencing. We also compared CD8+ T cell counts, pro-inflammatory cytokines levels, and nutritional status between the two groups. RESULTS: Compared to INRs with CD4 count > 200 cells/µL, those with CD4 count < 200 cells/µL had a lower CD4/CD8 ratio, lower nutritional status and higher serum levels of tumor necrosis factor (TNF)-α, interferon-γ-inducible protein (IP)-10 and interleukin (IL)-1α. Ruminococcaceae was less abundant in the CD4 count < 200 cells/µL group than in the CD4 count > 200 cells/µL group, and difference in alpha diversity was observed between the two groups. Moreover, CD4+ T cell counts were negatively associated with TNF-α and IL-1α levels and positively associated with the relative abundance of Ruminococcaceae. CONCLUSIONS: Our study demonstrated that lower CD4+ T cell counts in INRs are associated with a reduced abundance of Ruminococcaceae in the gut and elevated serum pro-inflammatory cytokines levels. Thus, interventions targeting gut microbiota to increase CD4+ T cell counts are a potential strategy for promoting immune reconstitution in HIV-infected INRs.

Heat-shock transcription factor 2 promotes sodium butyrate-induced autophagy by inhibiting mTOR in ulcerative colitis.

Butyrate-induced autophagy and anti-inflammatory effects of IECs plays an important role in UC. HSP has been proved to be associated with autophagy. HSF2, as an important regulator of HSP, has been determined to be highly expressed in UC. This study was designed to elucidate the relationship between HSF2, butyrate and epithelial autophagy and the potential mechanism of HSF2-related autophagy in UC. The autophagy levels and HSF2 expression in intestinal mucosa were increased in UC patients compared to controls. In DSS colitis models, hsf2-/- mice exhibited more severe intestinal inflammation and lower autophagy levels than wild-type mice. HSF2 expression could be induced by sodium butyrate and LPS as a dose-response relationship in HT-29 cells, epigenetically via increasing histone acetylation levels at the promoter region by sodium butyrate. Autophagy induced by sodium butyrate was promoted by overexpression HSF2 in HT-29 cells. Moreover, overexpression HSF2 decreased the expression and phosphorylation levels of PI3K, Akt and mTOR induced by sodium butyrate. HSF2 might induced by sodium butyrate and inflammation and played protective roles in UC by enhancing autophagy of IECs. This indicated that HSF2 may be a critical target for autophagy modulation and a new potential therapeutic target in UC.

A novel model with nutrition-related parameters for predicting overall survival of cancer patients.

BACKGROUND: Increasing evidence indicates that nutritional status could influence the survival of cancer patients. This study aims to develop and validate a nomogram with nutrition-related parameters for predicting the overall survival of cancer patients. PATIENTS AND METHODS: A total of 8749 patients from the multicentre cohort study in China were included as the primary cohort to develop the nomogram, and 696 of these patients were recruited as a validation cohort. Patients' nutritional status were assessed using the PG-SGA. LASSO regression models and Cox regression analysis were used for factor selection and nomogram development. The nomogram was then evaluated for its effectiveness in discrimination, calibration, and clinical usefulness by the C-index, calibration curves, and decision curve analysis. Kaplan-Meier survival curves were used to compare the survival rate. RESULTS: Seven independent prognostic factors were identified and integrated into the nomogram. The C-index was 0.73 (95% CI, 0.72 to 0.74) and 0.77 (95% CI, 0.74 to 0.81) for the primary cohort and validation cohort, which were both higher than 0.59 (95% CI, 0.58 to 0.61) of the TNM staging system. DCA demonstrated that the nomogram was higher than the TNM staging system and the TNM staging system combined with PG-SGA. Significantly median overall survival differences were found by stratifying patients into different risk groups (score < 18.5 and ≥ 18.5) for each TNM category (all Ps < 0.001). CONCLUSION: Our study screened out seven independent prognostic factors and successfully generated an easy-to-use nomogram, and validated and shown a better predictive validity for the overall survival of cancer patients.

Is hand grip strength a necessary supportive index in the phenotypic criteria of the GLIM-based diagnosis of malnutrition in patients with cancer?

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM) has the potential to gain global acceptance for diagnosing malnutrition. Of which, calf circumference (CC) was proposed as an alternative to evaluate the reduced muscle mass (RMM). The present study aimed to evaluate whether including the hand grip strength (HGS) was helpful for diagnosing malnutrition under the GLIM framework. METHODS: We performed a multicenter, observational cohort study including 3998 patients with cancer at two teaching hospitals. The RMM criterion was separately assessed using the calf circumference (CC), or the CC and HGS combined. Accordingly, two methods of GLIM diagnosis were independently developed to determine the nutritional status of the patients. The diagnostic concordance, baseline characteristics, and outcomes of patients were compared across the malnourished-CC-HGS, malnourished-CC+HGS, and well-nourished groups. The Patient-Generated Subjective Global Assessment (PG-SGA) was used as a comparator to identify the optimal method. RESULTS: Malnutrition was identified in 1120 (28%) patients by the CC method and 1060 (26.5%) patients by the CC+HGS method. Compared to the well-nourished group, the malnourished-CC+HGS group (60 patients, 1.5%) had poorer nutritional characteristics, poorer Karnofsky Performance Status scores, poorer global quality of life scores, and higher Nutritional Risk Screening 2002 scores. The severity of malnutrition diagnosed using the CC method (Kappa = 0.136) showed higher agreement with the PG-SGA than the CC+HGS method (Kappa = 0.127). CONCLUSION: Compared to CC+HGS, the CC alone appears to be adequate to evaluate RMM under the GLIM framework. A simpler method might facilitate the application of these criteria in clinical settings by increasing efficacy and minimizing missed diagnoses.

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.