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Background: The newly released Asian Working Group for Cachexia (AWGC) criteria share similar diagnostic items with the Global Leadership Initiative on Malnutrition (GLIM) criteria. This study aims to compare the AWGC cachexia and GLIM malnutrition in patients with gastric cancer and investigate whether one diagnosis continues to be a prognostic factor in individuals diagnosed with the other condition., Methods: Data of patients who underwent radical gastrectomy for gastric adenocarcinoma were prospectively collected from 2013 to 2019. The AWGC and GLIM criteria were applied to diagnosis cachexia and malnutrition, respectively. Univariate and multivariate logistic and Cox regression were used to verify the effect of relevant factors on postoperative complications and overall survival., Results: A total of 1420 patients were included, among whom 174 (12.3 %) were diagnosed with AWGC-cachexia alone, 85 (6.0 %) were diagnosed with GLIM-malnutrition alone, and 324 (22.8 %) had both AWGC-cachexia and GLIM-malnutrition. Both AWGC-cachexia and GLIM-malnutrition were independent risk factors for complications and overall survival. When they coexisted, the odds ratios (OR) and hazard ratios (HR) tended to be higher. In the AWGC-cachexia subset, GLIM-malnutrition remained an independent risk factor (HR = 1.544, 95 % CI = 1.098-2.171, P = 0.012) for overall survival after the adjustment of confounding factors. Similarly, in the GLIM-malnutrition subset, AWGC-cachexia remained an independent risk factor for overall survival (HR = 1.697, 95 % CI = 1.087-2.650, P = 0.020). Patients with both cachexia and malnutrition had the worst overall survival., Conclusion: AWGC-cachexia and GLIM-malnutrition criteria were two non-redundancy tools in reflecting mortality risk in preoperative nutritional assessment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment., (© 2024. The Author(s).)

Background: Cachexia is prevalent in cancer patients. The conventional diagnostic criteria for cachexia are often based on Western evidence, lacking consensus for Asian populations. This study aims to compare Asian Working Group for Cachexia (AWGC) criteria with Fearon's criteria, assessing their differences in population characteristics and prognostic impact., Methods: The clinical data of patients who underwent radical gastrectomy between 2013 and 2019 were prospectively collected. Cachexia diagnosis involves the utilization of either AWGC criteria and the previous international consensus proposed by Fearon et al. A scoring model is established based on the optional criteria according to the AWGC criteria. Univariate and multivariate logistic and Cox regression analysis were conducted to determine the independent effect factors for postoperative complications and overall survival., Results: In a total of 1330 patients, 461 met AWGC cachexia criteria and 311 met Fearon's criteria. Excluding 262 overlapping cases, those diagnosed solely with AWGC-cachexia had higher age and lower BMI, albumin, hemoglobin, and handgrip strength compared to those by Fearon's criteria alone. AWGC-cachexia independently increased the risk of postoperative complications, whereas Fearon's criteria did not. Patients with AWGC-cachexia also exhibited shorter overall survival than Fearon's criteria. The AWGC-based cachexia grading system effectively stratifies the risks of postoperative complications and mortality., Conclusions: The AWGC criteria is more effective in diagnosing cancer cachexia in the Asian population and provide better prognostic indicators., Competing Interests: Conflict of interest The authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objectives: Skeletal muscle index (SMI) is insufficient for evaluating muscle in obesity, and muscle attenuation (MA) may be a preferred indicator. This study aimed to investigate whether MA has greater prognostic value than SMI in gastric cancer patients with overweight and obesity., Methods: Clinical parameters of 1312 patients with gastric cancer who underwent radical gastrectomy were prospectively collected between 2013 and 2019. MA and SMI were analyzed by computed tomography scan. Overweight/obesity was defined as body mass index (BMI) ≥24 kg/m 2 . The hazard ratio (HR) for death was calculated using Cox regression analysis., Results: Among all patients, 405 were identified as overweight and obese, and 907 were identified as normal and underweight. MA was inversely associated with BMI and visceral fat area. Among the 405 patients with overweight and obesity, 212 patients (52%) were diagnosed with low MA. In the overweight/obese group, MA was an independent predictor for overall survival (HR, 1.610; P = 0.021) in multivariate Cox regression analyses, whereas SMI did not remain in the model. In the normal/underweight group, both low MA (HR, 1.283; P = 0.039) and low SMI (HR, 1.369; P = 0.008) were independent factors of overall survival. Additionally, 318 patients were identified as having visceral obesity in the overweight/obese group, and low MA was also an independent prognostic factor for survival in these patients (HR, 1.765; P = 0.013)., Conclusion: MA had a higher prognostic value than SMI in overweight and obese patients with gastric cancer after radical gastrectomy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cheng-Le Zhuang reports financial support was provided by National Natural Science Foundation of China. Cheng-Le Zhuang reports financial support was provided by Shanghai Chongming Science and Technology Commission. Su-Lin Wang reports financial support was provided by Basic Scientific Research Project of Wenzhou City. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Cancer cachexia is a debilitating condition with widespread negative effects. The heterogeneity of clinical features within patients with cancer cachexia is unclear. The identification and prognostic analysis of diverse phenotypes of cancer cachexia may help develop individualized interventions to improve outcomes for vulnerable populations. The aim of this study was to show that the machine learning-based cancer cachexia classification model generalized well on the external validation cohort., Methods: This was a nationwide multicenter observational study conducted from October 2012 to April 2021 in China. Unsupervised consensus clustering analysis was applied based on demographic, anthropometric, nutritional, oncological, and quality-of-life data. Key characteristics of each cluster were identified using the standardized mean difference. We used logistic and Cox regression analysis to evaluate 1-, 3-, 5-y, and overall mortality., Results: A consensus clustering algorithm was performed for 4329 patients with cancer cachexia in the discovery cohort, and four clusters with distinct phenotypes were uncovered. From clusters 1 to 4, the clinical characteristics of patients showed a transition from almost unimpaired to mildly, moderately, and severely impaired. Consistently, an increase in mortality from clusters 1 to 4 was observed. The overall mortality rate was 32%, 40%, 54%, and 68%, and the median overall survival time was 21.9, 18, 16.7, and 13.6 mo for patients in clusters 1 to 4, respectively. Our machine learning-based model performed better in predicting mortality than the traditional model. External validation confirmed the above results., Conclusions: Machine learning is valuable for phenotype classifications of patients with cancer cachexia. Detection of clinically distinct clusters among cachexic patients assists in scheduling personalized treatment strategies and in patient selection for clinical trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Adult skeletal muscle regeneration is mainly driven by muscle stem cells (MuSCs), which are highly heterogeneous. Although recent studies have started to characterize the heterogeneity of MuSCs, whether a subset of cells with distinct exists within MuSCs remains unanswered. Here, we find that a population of MuSCs, marked by Gli1 expression, is required for muscle regeneration. The Gli1 + MuSC population displays advantages in proliferation and differentiation both in vitro and in vivo. Depletion of this population leads to delayed muscle regeneration, while transplanted Gli1 + MuSCs support muscle regeneration more effectively than Gli1- MuSCs. Further analysis reveals that even in the uninjured muscle, Gli1 + MuSCs have elevated mTOR signaling activity, increased cell size and mitochondrial numbers compared to Gli1 - MuSCs, indicating Gli1 + MuSCs are displaying the features of primed MuSCs. Moreover, Gli1 + MuSCs greatly contribute to the formation of G Alert cells after muscle injury. Collectively, our findings demonstrate that Gli1 + MuSCs represents a distinct MuSC population which is more active in the homeostatic muscle and enters the cell cycle shortly after injury. This population functions as the tissue-resident sentinel that rapidly responds to injury and initiates muscle regeneration., (© 2023. The Author(s).)

Sarcopenia is a progressive systemic skeletal muscle disorder characterized by a pathological decline in muscle strength, quantity, and quality, which frequently affects the elderly population. The majority of cancer patients are of advanced age. Patients may already have sarcopenia prior to cancer development, and those with cancer are prone to developing sarcopenia due to hypercatabolism, inflammation, reduced physical fitness, anorexia, adverse effects, and stress associated with anticancer therapy. Based on the timing, sarcopenia in patients with cancer can be categorized into three: pre-existing sarcopenia before the onset of cancer, sarcopenia related to cancer, and sarcopenia related to cancer treatment. Sarcopenia not only changes the body composition of patients with cancer but also increases the incidence of postoperative complications, reduces therapeutic efficacy, impairs quality of life, and results in shortened survival. Different therapeutic strategies are required to match the cancer status and physical condition of patients with different etiologies and stages of sarcopenia. Here, we present a comprehensive review of the epidemiology and diagnosis of sarcopenia in patients with cancer, elucidate the complex interactions between cancer and sarcopenia, and provide evidence-based strategies for sarcopenia management in these patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Excessive inflammatory response is a critical pathogenic factor for the tissue damage and organ failure caused by systemic inflammatory response syndrome (SIRS) and sepsis. In recent years, drugs targeting RIPK1 have proved to be an effective anti-inflammatory strategy. In this study, we identified a novel anti-inflammatory lead compound 4-155 that selectively targets RIPK1. Compound 4-155 significantly inhibited necroptosis of cells, and its activity is about 10 times higher than the widely studied Nec-1 s. The anti-necroptosis effect of 4-155 was mainly dependent on the inhibition of phosphorylation of RIPK1, RIPK3, and MLKL. In addition, we demonstrated that 4-155 specifically binds RIPK1 by drug affinity responsive target stability (DARTS), immunoprecipitation, kinase assay, and immunofluorescence microscopy. More importantly, compound 4-155 could inhibit excessive inflammation in vivo by blocking RIPK1-mediated necroptosis and not influence the activation of MAPK and NF-κB, which is more potential for the subsequent drug development. Compound 4-155 effectively protected mice from TNF-induced SIRS and sepsis. Using different doses, we found that 6 mg/kg oral administration of compound 4-155 could increase the survival rate of SIRS mice from 0 to 90%, and the anti-inflammatory effect of 4-155 in vivo was significantly stronger than Nec-1 s at the same dose. Consistently, 4-155 significantly reduced serum levels of pro-inflammatory cytokines (TNF-α and IL-6) and protected the liver and kidney from excessive inflammatory damages. Taken together, our results suggested that compound 4-155 could inhibit excessive inflammation in vivo by blocking RIPK1-mediated necroptosis, providing a new lead compound for the treatment of SIRS and sepsis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Although previous studies have implicated the negative outcomes of sarcopenia, evidence is limited to one or a few types of cancer. The aim of this study was to evaluate the distribution and influencing factors of sarcopenia, and explore the relationship between sarcopenia and cancer prognosis in a large oncological population., Methods: This observational cohort study included patients diagnosed with malignant cancer between May 2011 and January 2019. Hematologic and anthropometric parameters were collected prospectively. Low skeletal muscle mass and radiodensity were diagnosed using clinical indicators, according to the two prediction models. The importance of potential risk factors for sarcopenia was estimated by subtracting the predicted degrees of freedom from the partial χ 2 statistic. Hazard rates of death were calculated using the hazard function and Cox regression analyses., Results: We included 13 761 patients with cancer; the prevalence of sarcopenia was 33%. The median age was 58 y and 7135 patients (52%) were men. Patients with sarcopenia had a worse nutritional status and quality of life than those without sarcopenia. Age was the most important risk factor for sarcopenia compared with body mass index or TNM stage. Additionally, patients with sarcopenia had a significantly higher and earlier peak risk for mortality. After adjusting for baseline characteristics, sarcopenia was independently associated with mortality in the research population (hazard ratio, 1.429; P < 0.001) and most cancer types., Conclusion: Age is the most important risk factor for sarcopenia even in patients with cancer. Sarcopenia is strongly associated with a poor quality of life and reduced overall survival., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Purpose: Necroptosis plays an essential role in acute kidney injury and is mediated by receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed lineage kinase domain-like pseudokinase (MLKL). A novel RIPK3 inhibitor, compound 42 (Cpd-42) alleviates the systemic inflammatory response. The current study was designed to investigate whether Cpd-42 exhibits protective effects on acute kidney injury and reveal the underlying mechanisms., Experimental Approach: The effects of Cpd-42 were determined in vivo through cisplatin- and ischaemia/reperfusion (I/R)-induced acute kidney injury and in vitro through cisplatin- and hypoxia/re-oxygenation (H/R)-induced cell damage. Transmission electron microscopy and periodic acid-Schiff staining were used to identify renal pathology. Cellular thermal shift assay and RIPK3-knockout mouse renal tubule epithelial cells were used to explore the relationship between Cpd-42 and RIPK3. Molecular docking and site-directed mutagenesis were used to determine the binding site of RIPK3 with Cpd-42., Key Results: Cpd-42 reduced human proximal tubule epithelial cell line (HK-2) cell damage, necroptosis and inflammatory responses in vitro. Furthermore, in vivo, cisplatin- and I/R-induced acute kidney injury was alleviated by Cpd-42 treatment. Cpd-42 inhibited necroptosis by interacting with two key hydrogen bonds of RIPK3 at Thr94 and Ser146, which further blocked the phosphorylation of RIPK3 and mitigated acute kidney injury., Conclusion and Implications: Acting as a novel RIPK3 inhibitor, Cpd-42 reduced kidney damage, inflammatory response and necroptosis in acute kidney injury by binding to sites Thr94 and Ser146 on RIPK3. Cpd-42 could be a promising treatment for acute kidney injury., (© 2023 British Pharmacological Society.)

Ferroptosis is increasingly being recognized as a key element in the pathogenesis of diverse diseases. Recent studies have highlighted the intricate links between iron metabolism and neurodegenerative disorders. Emerging evidence suggests that iron homeostasis, oxidative stress, and neuroinflammation all contribute to the regulation of both ferroptosis and neuronal health. However, the precise molecular mechanisms underlying the involvement of ferroptosis in the pathological processes of neurodegeneration and its impact on neuronal dysfunction remain incompletely understood. In our Review, we provide a comprehensive analysis and summary of the potential molecular mechanisms underlying ferroptosis in neurodegenerative diseases, aiming to elucidate the disease progression of neurodegeneration. Additionally, we discuss potential therapeutic agents that modulate ferroptosis with the goal of identifying novel drug molecules for the treatment of neurodegenerative disorders.

Ferroptosis is a new form of regulated cell death characterized by excessive iron accumulation and uncontrollable lipid peroxidation. The role of ferroptosis in metabolic dysfunction-associated fatty liver disease (MAFLD) is not fully elucidated. In this study we compared the therapeutic effects of ferroptosis inhibitor liproxstatin-1 (LPT1) and iron chelator deferiprone (DFP) in MAFLD mouse models. This model was established in mice by feeding a high-fat diet with 30% fructose in water (HFHF) for 16 weeks. The mice then received LPT1 (10 mg·kg -1 ·d -1 , ip) or DFP (100 mg·kg -1 ·d -1 , ig) for another 2 weeks. We showed that both LPT1 and DFP treatment blocked the ferroptosis markers ACSL4 and ALOX15 in MAFLD mice. Furthermore, LPT1 treatment significantly reduced the liver levels of triglycerides and cholesterol, lipid peroxidation markers 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), and ameliorated the expression of lipid synthesis/oxidation genes (Pparα, Scd1, Fasn, Hmgcr and Cpt1a), insulin resistance, mitochondrial ROS content and liver fibrosis. Importantly, LPT1 treatment potently inhibited hepatic apoptosis (Bax/Bcl-xL ratio and TUNEL + cell number), pyroptosis (cleavages of Caspase-1 and GSDMD) and necroptosis (phosphorylation of MLKL). Moreover, LPT1 treatment markedly inhibited cleavages of PANoptosis-related caspase-8 and caspase-6 in MAFLD mouse liver. In an in vitro MAFLD model, treatment with LPT1 (100 nM) prevented cultured hepatocyte against cell death induced by pro-PANoptosis molecules (TNF-α, LPS and nigericin) upon lipid stress. On the contrary, DFP treatment only mildly attenuated hepatic inflammation but failed to alleviate lipid deposition, insulin resistance, apoptosis, pyroptosis and necroptosis in MAFLD mice. We conclude that ferroptosis inhibitor LPT1 protects against steatosis and steatohepatitis in MAFLD mice, which may involve regulation of PANoptosis, a coordinated cell death pathway that involves apoptosis, pyroptosis and necroptosis. These results suggest a potential link between ferroptosis and PANoptosis., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Purpose: Malnutrition is common in the patients with gastric cancer. Radical gastrectomy remained the primary strategy of curable treatment for gastric cancer. This study is performed to explore the effect of laparoscopic radical gastrectomy on clinical outcomes in gastric cancer patients with malnutrition., Methods: Gastric cancer patients with GLIM-defined malnutrition between 2014 and 2019 at our center were enrolled. The patients were divided into two groups according to the different type of surgery. Propensity score match analysis was used to balance the clinicopathologic characteristics of two groups. Postoperative outcomes and survival were compared. Multivariate analysis was used to independent risk factors of complication, overall survival (OS), and disease-free survival (DFS)., Results: Compared with patients underwent open radical gastrectomy, patients who underwent laparoscopic radical gastrectomy had lower rate of total, surgical and severe complications. They also had shorter postoperative hospital stay with better OS and DFS. Hypoalbuminemia (P = 0.003) was the independent risk factor of complications. Old age (≥75, P = 0.035) and TNM stage (III: P < 0.001, II: P = 0.015) were the independent risk factors of OS. Combined resection (P = 0.003) and TNM stage (III: P < 0.001, II: P = 0.001) posed independent risk factors of lacking DFS. Laparoscopic surgery proved to be the independent protective factor of complications (P = 0.014), OS (P < 0.001) and DFS (P < 0.001)., Conclusion: Laparoscopic radical gastrectomy was relative safe and showed favorable outcomes in malnourished gastric cancer patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Cannabinoid receptors belong to the large family of G-protein-coupled receptors, which can be divided into two receptor types, cannabinoid receptor type-1 (CB1) and cannabinoid receptor type-2 (CB2). Marinol, Cesamet and Sativex are marketed CB1 drugs which are still in use and work well, but the central nervous system side effects caused by activation CB1, which limited the development of CB1 ligands. So far, no selective CB2 ligand has been approved for marketing, but lots of its ligands in the clinical stage and pre-clinical stage have positive effects on the treatment of some disease models and have great potential for development. Most selective CB2 agonists are designed and synthesized based on non-selective CB2 agonists through the classical med-chem strategies, e.g. molecular hybridization, scaffold hopping, bioisosterism, etc. During these processes, the balance between selectivity, activity, and pharmacokinetic properties needs to be achieved. Hence, we summarized some reported ligands on the basis of the optimization strategies in recent 10 years, and the limitations and future directions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Skeletal muscle plays a critical role in human health. Muscle stem cells (MuSCs) serve as the major cell type contributing to muscle regeneration by directly differentiating to mature muscle cells. MuSCs usually remain quiescent with occasionally self-renewal and are activated to enter cell cycle for proliferation followed by differentiation upon muscle injury or under pathological conditions. The quiescence maintenance, activation, proliferation, and differentiation of MuSCs are tightly regulated. The MuSC cell-intrinsic regulatory network and the microenvironments work coordinately to orchestrate the fate transition of MuSCs. The heterogeneity of MuSCs further complicates the regulation of MuSCs. This review briefly summarizes the current progress on the heterogeneity of MuSCs and the microenvironments, epigenetic, and transcription regulations of MuSCs., (© 2022. The Author(s).)

Aging is characterized by a progressive deterioration of physiological integrity, leading to impaired functional ability and ultimately increased susceptibility to death. It is a major risk factor for chronic human diseases, including cardiovascular disease, diabetes, neurological degeneration, and cancer. Therefore, the growing emphasis on "healthy aging" raises a series of important questions in life and social sciences. In recent years, there has been unprecedented progress in aging research, particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes. In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases, we review the descriptive, conceptual, and interventive aspects of the landscape of aging composed of a number of layers at the cellular, tissue, organ, organ system, and organismal levels., (© 2022. Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Myosteatosis and sarcopenia are forms of muscle depletion that impair the normal physiological function of elderly patients, resulting in a worse prognosis. This study aimed to evaluate the prognostic value of sarcopenia and myosteatosis on postoperative outcomes in elderly patients with colorectal cancer., Methods: From February 2015 to March 2021, a total of 921 elderly patients who underwent curative surgeries for colorectal cancer at 2 centers were enrolled and grouped by the presence of either myosteatosis or sarcopenia. Clinicopathological characteristics and postoperative outcomes were compared between the 2 groups. The independent risk factors for complications and overall survival were evaluated., Results: Patients with myosteatosis had higher incidences of total and surgical complications, longer surgical duration, lower numbers of lymph nodes harvested, and longer postoperative hospital stays. Patients with sarcopenia had higher incidences of total complications, medical complications, and shorter surgical durations. Both conditions had adverse effects on overall survival and disease-free survival. Overweight status (P = .004), hypoalbuminemia (P < .001), myosteatosis, (P = .029) and sarcopenia (P = .017) were independent risk factors for total complications. Hypoalbuminemia (P = .035), myosteatosis (P = .003), sarcopenia (P = .027), and tumor-nodes-metastasis stage (≥Ⅲ; P < .001) were independent negative prognostic factors for overall survival., Conclusion: Myosteatosis and sarcopenia have different characteristics and are associated with poor prognoses in elderly patients with colorectal cancer. Myosteatosis occurs more frequently. Early diagnosis and intervention for myosteatosis should be included in preoperative management, which may improve prognosis in elderly patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Malnutrition and sarcopenia are common in elderly gastric cancer patients, which are also interrelated and affect each other. We aimed to determine the characteristics of coexistence of malnutrition and sarcopenia in the elderly gastric cancer patients and investigate the predictive roles of malnutrition and sarcopenia on clinical outcomes., Methods: Between 2014 and 2019, a total of 742 elderly gastric cancer patients were enrolled. Malnutrition and sarcopenia were diagnosed according to the most recent diagnostic criteria. Patients were divided into four groups according to presence of these two symptoms. Clinical characteristics, short- and long-term outcomes were compared among four groups. The independent risk factors for complications and survival were evaluated using univariate and multivariate analyses., Results: Of all patients, 34.8% were diagnosed with malnutrition and 34.0% were diagnosed with sarcopenia. Patients with both malnutrition and sarcopenia had the highest rate of total ( P < 0.001), surgical ( P = 0.003), and medical complications ( P = 0.025), and the highest postoperative hospital stays ( P < 0.001) and hospitalization costs ( P < 0.001). They also had the worst overall survival ( P < 0.0001) and disease-free survival ( P < 0.0001). Sarcopenia and Charlson Comorbidity Index (≥2) were independent risk factors for total complications. Hypoalbuminemia and malnutrition were non-tumor-related independent risk factors for overall survival and disease-free survival., Conclusions: Malnutrition and sarcopenia had superimposed negative effects on elderly gastric cancer patients. Preoperative geriatric evaluation including screening for malnutrition and sarcopenia are recommended for all elderly gastric cancer patients for accurate treatment strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Zhang, Zhang, Yu, Chen, Lin, Dong, Zhuang and Yu.)

Objective: Anthropometric measurements including body mass index (BMI), mid-upper arm circumference (MUAC), and calf circumference (CC) are simple and convenient indicators of nutritional status and muscle mass. However, most of their reference values come from studies based on healthy Western populations. The optimal reference values of these anthropometric factors in Asian patients with cancer are unclear. The aim of this study was to develop reference values of severely and moderately low BMI, MUAC, and CC by analyzing a large sample of patients with cancer from a nationwide population., Methods: We conducted a retrospective analysis of 16 104 patients who were diagnosed with malignant diseases from June 2012 to January 2019. The median age of the patients was 58 y, and 52.5% were men. Optimal stratification was used to calculate reference values using X-tile software. Kaplan-Meier and multivariate Cox analysis were performed to analyze survival data. A receiver operating characteristic analysis was conducted to test the performance of new reference values in diagnosing malnutrition., Results: The optimal reference values were calculated for BMI (moderately low: 19.7 [women] and 19 [men]; severely low: 16.7 [women] and 16.7 [men]), MUAC (moderately low: 24.5 [women] and 23.2 [men] severely low: 20.6 [women] and 19.4 [mnen]), and CC (moderately low: 29.1 [women] and 29.3 [men]; severely low: 26.7 [women] and 26.9 [men]). New reference values had more significant affects on mortality risk and better performance in predicting malnutrition than existing ones., Conclusions: The present study defined reference values of moderately and severely low BMI, MUAC, and CC, which showed strong associations with quality of life, malnutrition, and mortality risk. New reference values from the present study are classification references specifically for the Asian population, which is a new step to promote the application of Global Leadership Initiative on Malnutrition criteria and its severity grading system in Asia., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Sarcopenia and cachexia are two predictors of adverse clinical outcomes, but they are partly overlapping. We aimed to compare the characteristics and prognostic value of cachexia and sarcopenia in patients after gastrectomy., Methods: From 2014 to 2019, a total of 1215 gastric cancer patients were enrolled. Cachexia and sarcopenia were diagnosed according to the most recent consensus definitions. Baseline characteristics and clinical outcomes were compared between the two groups. Risk factors of survival were evaluated by Cox regression analysis., Results: Of all patients, 26.5% were diagnosed with cachexia and 19.8% were diagnosed with sarcopenia. Sarcopenia was more prevalent in elderly patients, while cachexia was prone to occur in patients with TMN stage III. Survival curves showed that sarcopenia had adverse effects in patients with TMN stage I and II-III, while cachexia was only associated with poor survival at stages II-III. For the entire cohort, both cachexia and sarcopenia were adverse factors for prognosis. However, for stage I patients, sarcopenia was an independent predictor for overall survival (OS) (HR = 4.939, P < 0.001) and disease-free survival (DFS) (HR = 4.256, P < 0.001), but not cachexia; for stage II-III patients, cachexia was an independent predictor for OS (HR = 1.538, P < 0.001) and DFS (HR = 1.473, P = 0.001), but not sarcopenia., Conclusions: Sarcopenia and cachexia have different clinical characteristics and prognostic values. For patients with early stage gastric cancer, detection for sarcopenia was more meaningful than cachexia. However, the prognostic significance of cachexia exceeded sarcopenia in advanced cancer., (© 2021. Society of Surgical Oncology.)

Background: The relationships between sarcopenia and postoperative outcomes in patients with early-stage gastric cancer who undergo radical gastrectomy is unclear. We aimed to investigate the predictive value of sarcopenia on adverse outcomes for stage I gastric cancer., Methods: The clinical data of patients who underwent radical gastrectomy for stage I gastric cancer between July 2013 and May 2019 were prospectively collected. Basic sarcopenia components were measured preoperatively. Univariate and multivariate analyses were conducted to evaluate the risk factors for short- and long-term outcomes., Results: A total of 507 patients with early-stage gastric cancer were included in the study, and 73 (14.4%) patients were diagnosed as sarcopenia. Patients with sarcopenia had significantly higher incidence of postoperative complications (32.9% vs. 17.5%, P = 0.002), longer postoperative hospital stays (13 days vs. 12 days, P < 0.001), higher hospitalization costs (65210 yuan vs. 55197 yuan, P < 0.001) and one-year mortality (8.2% vs. 1.8%, P = 0.002). During the median follow-up time of 38.8 months, 12 (16.4%) patients dead in the sarcopenic group and 25 (5.8%) patients dead in the non-sarcopenic group. Sarcopenia was an independent risk factor for both short- and long-term clinical outcomes. Moreover, we found that low muscle quantity and low handgrip strength mediated the adverse impacts of sarcopenia on postoperative complications while low muscle quality mediated the adverse impacts of sarcopenia on overall survival., Conclusion: Sarcopenia was strongly associated with worse short- and long-term clinical outcomes in patients with stage I gastric cancer who undergo radical gastrectomy., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Coronavirus Disease 2019 (COVID-19) infected by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been declared a public health emergency of international concerns. Cytokine storm syndrome (CSS) is a critical clinical symptom of severe COVID-19 patients, and the macrophage is recognized as the direct host cell of SARS-CoV-2 and potential drivers of CSS. In the present study, peramivir was identified to reduce TNF-α by partly intervention of NF-κB activity in LPS-induced macrophage model. In vivo , peramivir reduced the multi-cytokines in serum and bronchoalveolar lavage fluid (BALF), alleviated the acute lung injury and prolonged the survival time in mice. In human peripheral blood mononuclear cells (hPBMCs), peramivir could also inhibit the release of TNF-α. Collectively, we proposed that peramivir might be a candidate for the treatment of COVID-19 and other infections related CSS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Tu, Sun, Chen, Zhang, Zhuang, Wang and Su.)

Background: Completing Patient-Generated Subjective Global Assessment (PG-SGA) questionnaires is time consuming. This study aimed to develop and validate an easy-to-use modified PG-SGA (mPG-SGA) for cancer patients., Methods: Seventy professionals assessed the content validity, comprehensibility, and difficulty of the full PG-SGA. A survey including the PG-SGA and other questionnaires was completed by 34 071 adult hospitalized cancer patients with first cancer diagnosis or recurrent disease with any tumour comorbidities from the INSCOC study. Among them, 1558 patients were followed for 5 years after admission. Reliability and rank correlation were estimated to assess the consistency between PG-SGA items and to select mPG-SGA items. The external and internal validity, test-retest reliability, and predictive validity were tested for the mPG-SGA via comparison with both the PG-SGA and abridged PG-SGA (abPG-SGA)., Results: After deleting items that more than 50% of professionals considered difficult to evaluate (Worksheet 4) and items with an item-total correlation <0.1, the mPG-SGA was constructed. Nutritional status was categorized using mPG-SGA scores as well-nourished (0 points) or mildly (1-2 points), moderately (3-6 points), or severely malnourished (≥7 points) based on the area under curve (0.962, 0.989, and 0.985) and maximal sensitivity (0.924, 0.918, and 0.945) and specificity (1.000, 1.000, and 0.938) of the cut-off scores. The external and internal validity and test-retest reliability were good. Significant median overall survival differences were found among nutritional status groups categorized by the mPG-SGA: 24, 18, 14, and 10 months for well-nourished, mildly malnourished, moderately malnourished, and severely malnourished, respectively (all Ps < 0.05). Neither the PG-SGA nor the abridged PG-SGA could discriminate the median overall survival differences between the well-nourished and mildly malnourished groups., Conclusions: We systematically developed and validated the mPG-SGA as an easier-to-use nutritional assessment tool for cancer patients. The mPG-SGA appears to have better predictive validity for survival than the PG-SGA and abridged PG-SGA., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Concerns about vaccine safety are an important reason for vaccine hesitancy, however, limited information is available on whether common adverse reactions following vaccination affect the immune response. Data from three clinical trials of recombinant vaccines were used in this post hoc analysis to assess the correlation between inflammation-related solicited adverse reactions (ISARs, including local pain, redness, swelling or induration and systematic fever) and immune responses after vaccination. In the phase III trial of the bivalent HPV-16/18 vaccine (Cecolin®), the geometric mean concentrations (GMCs) for IgG anti-HPV-16 and -18 ( P <0.001) were significantly higher in participants with any ISAR following vaccination than in those without an ISAR. Local pain, induration, swelling and systemic fever were significantly correlated with higher GMCs for IgG anti-HPV-16 and/or anti-HPV-18, respectively. Furthermore, the analyses of the immunogenicity bridging study of Cecolin® and the phase III trial of a hepatitis E vaccine yielded similar results. Based on these results, we built a scoring model to quantify the inflammation reactions and found that the high score of ISAR indicates the strong vaccine-induced antibody level. In conclusion, this study suggests inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.

Background and Aims: Sarcopenia is negatively associated with clinical outcomes. However, the definitions of sarcopenia are inconsistent across international consensuses. Thus, the purpose of this study is to compare the impact of the basic definition components of sarcopenia and their combinations in post-operative complications and overall survival, aiming to find the best sarcopenia definition to stratify the prognosis in an Asian population. Methods: A total of 1,307 patients who underwent curative surgery for gastric cancer from July 2014 to May 2019 were prospectively included. The basic sarcopenia components were measured pre-operatively, including low skeletal muscle mass index (LSMI), low skeletal muscle radiodensity (LSMD), low handgrip strength (LHGS), and low gait speed (LGS). Among them, LSMI and LSMD were measured using a CT post-processing software, LHGS was measured using an electronic hand dynamometer, and LGS was represented by a 6-m walk speed. Results: For the single basic component, the muscle function parameters (LHGS or LGS) but not the muscle composition parameters (LSMI or LSMD) showed associations with post-operative complications and mortality. For the combination of the basic combinations, all statistically significant combinations included at least one muscle function parameter. The combination of muscle composition (LSMI or LSMD) and muscle function (LHGS or LGS) had a significantly higher area under the curve in the prediction of post-operative complications compared with the combinations of two muscle function parameters (LSMI plus LSMD) or two muscle composition parameters (LHGS plus LGS). Conclusions: Compared with muscle composition parameters (LSMI and LSMD), muscle function parameters (LHGS and LGS) are better predictors of post-operative complications and overall survival, which should be considered as the principal determinant in the sarcopenia definition. The definition of sarcopenia consists of muscle function (LHGS or LGS) and muscle composition (LSMI or LSMD) separately, which is better than the combination of the two muscle function parameters (LHGS plus LGS) or two muscle composition parameters (LSMI plus LSMD)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Zhang, Shi, Zhang, Wang, Shen, Chen, Shen, Yu and Zhuang.)

Background: Patients with gastric cancer often suffer from generalized and progressive reduction of skeletal muscle mass and strength, which negatively affects the quality of life (QOL). In this study, we explored the impact of sarcopenia on QOL and overall survival (OS)., Methods: From December 2015 to June 2017, 135 patients underwent radical gastrectomy at the First Affiliated Hospital of Wenzhou Medical University. Based on the diagnostic criteria of the Asian Working Group for Sarcopenia (AWGS), data including handgrip strength, 6-m gait speed and muscle mass were collected and analyzed. EORTC QLQ-C30 and EORTC QLQ-STO22 were used to evaluate the QOL before surgery, 1, 3 and 6 months after surgery., Results: A total of 27 out of the 135 patients (20.00%) were diagnosed with sarcopenia. Compared with non-sarcopenia group, patients in sarcopenia group had a higher incidence of postoperative complications (14.80% vs. 40.70%, p = 0.003), and more hospitalization costs (p = 0.029). The scores of eating restriction (p = 0.026), anxiety (p = 0.045) and body image (p = 0.046) were significantly higher in sarcopenia group at postoperative 6 months. Besides, sarcopenia was an independent risk factor for global health status at 6 months after operation (OR: 2.881, 95% CI: 1.110-7.475, p = 0.030) and OS (HR: 3.140, 95% CI: 1.255-7.855, p = 0.014). Other factors, including tumor stage III and the postoperative complications, had negative influences on OS., Conclusion: Sarcopenia is a predictive factor of poor QOL and prognosis in patients with gastric cancer., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: The aim of this study was to determine the feasibility of substituting handgrip strength (HGS) for muscle mass as a constituent in the Global Leadership Initiative on Malnutrition (GLIM) to diagnose malnourished patients with gastrointestinal (GI) cancer., Methods: The study included 2209 patients diagnosed with GI cancer from two centers. All patients were evaluated for nutritional risk using Nutritional Risk Screening 2002 within 24 h of admission. The GLIM consensus was then used to diagnose malnourished patients. The evaluation of muscle mass as one of the constituents contained in the GLIM consensus was measured by computed tomography presented as skeletal muscle mass index (SMI) and HGS, respectively. Consistency test was carried out to evaluate the diagnostic value of SMI and HGS., Results: There were 1042 (47.2%) cases of gastric cancer and 1167 (52.8%) cases of colorectal cancer. Among these cases were 768 patients (34.8%) at nutritional risk. Furthermore, 603 (27.3%) and 593 patients (26.8%) were diagnosed with malnutrition in the GLIM (SMI) group and the GLIM (HGS) group, respectively, and 544 (24.6%) patients in the two groups overlapped. The consistency test results showed that the κ value in the GLIM (HGS) group compared with the GLIM (SMI) group was 0.881 (P < 0.001) in patients with gastric cancer and 0.872 (P < 0.001) in those with colorectal cancer., Conclusion: HGS can be a substitute for muscle mass as a constituent in the diagnostic criteria of GLIM in patients with GI cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The applicability of laparoscopic-assisted radical gastrectomy for elderly patients with gastric cancer is still not well clarified. The aim of this double-center study was to explore the feasibility and effectiveness of laparoscopic-assisted radical gastrectomy on elderly patients with gastric cancer., Methods: We prospectively collected data of patients who underwent gastrectomy for cancer in two centers from June 2016 to December 2019. Propensity score matching was performed at a ratio of 1:1 to compare the laparoscopic-assisted radical gastrectomy group and open radical gastrectomy group. Univariate analyses and multivariate logistic regression analyses evaluating the risk factors for total, surgical, and medical complications were performed., Results: A total of 481 patients with gastric cancer met the inclusion criteria and were included in this study. After propensity score analysis, 258 patients were matched each other (laparoscopic-assisted radical gastrectomy (LAG) group, n = 129; open radical gastrectomy (OG) group, n = 129). LAG group had lower rate of surgical complications (P = 0.009), lower rate of severe complications (P = 0.046), shorter postoperative hospital stay (P = 0.001), and lower readmission rate (P = 0.039). Multivariate analyses revealed that anemia, Charlson comorbidity index, and combined resection were independent risk factors in the LAG group, whereas body mass index and American Society of Anesthesiology grade in the OG group., Conclusion: Laparoscopic-assisted radical gastrectomy was relative safe even effective in elderly gastric cancer patients. We should pay attention to the different risk factors when performing different surgical procedures for gastric cancer in elderly patients.

Background: The skeletal muscle mass index (SMI) and skeletal muscle radiodensity (SMD) are important components of sarcopenia and malnutrition. However, their assessment requires additional resources in cancer patients, which is inconvenient for the early detection of sarcopenia and malnutrition., Objectives: This study aimed to develop and validate nomograms for the prediction of low muscle mass and muscle radiodensity and to examine the application value of the nomograms in the diagnoses of sarcopenia and malnutrition., Methods: A total of 1315 patients diagnosed with gastric cancer between July 2014 and May 2019 were included. Random resampling with an 80/20 split ratio was performed to obtain a training cohort (n = 1056) and a validation cohort (n = 259). Nomograms were separately constructed for low SMI (LSMI) and low SMD (LSMD) in the training cohort based on prospectively collected preoperative data. The performance of the nomograms was assessed using the AUC, calibration curve, and Hosmer-Lemeshow test. The application values of the nomograms in the diagnoses of sarcopenia and malnutrition were also evaluated., Results: Age, BMI, hemoglobin concentration, and gait speed were included in the nomogram for LSMI predictions. These variables, in addition to sex, were included in the nomogram for LSMD predictions. The diagnostic nomograms exhibited good discrimination, with AUCs of 0.818 (95% CI, 0.791-0.845) for the LSMI nomogram and 0.788 (95% CI, 0.761-0.815) for the LSMD diagnostic nomogram in the training cohort. Calibration was also excellent. The agreement ratios between the nomograms and actual observations in the total population were 92.3% and 95.6% for sarcopenia and malnutrition, respectively. Prognostic nomograms exhibited similar performance in the validation cohort., Conclusions: Diagnostic nomograms consisting of preoperative factors can successfully predict LSMI and LSMD. These models facilitate early identification and timely interventions for at-risk populations., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

A DNA-encoded library is a collection of small molecules covalently linked to DNA that has unique information about the identity and the structure of each library member. A DNA-encoded chemical library (DEL) is broadly adopted by major pharmaceutical companies and used in numerous drug discovery programs. The application of the DEL technology is advantageous at the initial period of drug discovery because of reduced cost, time, and storage space for the identification of target compounds. The key points for the construction of DELs comprise the development and the selection of the encoding methods, transfer of routine chemical reaction from off-DNA to on-DNA, and exploration of new chemical reactions on DNA. The limitations in the chemical space and the diversity of DEL were reduced gradually by using novel DNA-compatible reactions based on the formation and the cleavage of various bonds. Here, we summarized a series of novel DNA-compatible chemistry reactions for DEL building blocks and analysed the druggability of screened hit molecules via DELs in the past five years., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: In patients with ultralow rectal cancer, surgical resection of the tumor without impairing sphincter function remains a technical challenge. The purpose of this study was to describe a new technique of transanal natural orifice specimen extraction (NOSE) surgery using our independently developed devices, aiming to achieve precise cancer resection and preserve sphincter function in patients with ultralow rectal cancer., Methods: Precision functional sphincter-preserving surgery (PPS) was performed on nineteen patients with ultralow rectal cancer between June 2019 and April 2020. With the help of our independently developed devices, surgeons directly and accurately removed the lower edge of the tumor and retained healthy rectal tissue on the nontumorous side. Hand-sewn anastomosis with a mattress suture was used to achieve sturdy anastomosis. Preoperative baseline characteristics, operative details, 90-day postoperative complications, costs, and anal function score at 6 months after surgery were documented., Results: Nineteen ultralow rectal cancer patients with a median distance to the dentate line of 2.0 cm successfully underwent PPS without serious postoperative complications. Six out of nineteen patients (31.6%) received a prophylactic stoma. The average cost was 62164.1 yuan. At 6 months after surgery, the average Wexner anal function score and the average Vaizey score were both 3 points., Conclusions: PPS can be employed to precisely resect rectal tumors and preserve sphincter function in ultralow rectal cancer patients. The use of our devices enhanced surgical efficiency, reduced the need for prophylactic stoma, reduced surgery-related costs, and prevented abdominal surgical incisions.

Background: Handgrip strength (HGS) is associated with poor clinical outcomes, including all-cause, non-cardiovascular, and cardiovascular mortalities. The published cut-off points for HGS are mostly based on community populations from Western countries, lacking information on cancer patients from China. The objective of this study was to establish sex-specific cut-off points for Chinese cancer patients and investigate the effect of low HGS on cancer mortality., Methods: We did a retrospective cohort study of patients who were diagnosed with malignant cancer from June 2012 to December 2018. HGS was measured using a hand dynamometer in 8257 cancer patients. Optimal stratification was used to solve threshold points. The hazard ratio (HR) of all cancer mortality and cancer-specific mortality was calculated using Cox proportional hazard regression models., Results: Among all participants, there were 3902 (47.3%) women and 4355 (52.7%) men. The median age was 58 years old. The cut-off points of HGS to best classify patients with respect to time to mortality were <16.1 kg for women and <22 kg for men. Low HGS was associated with overall cancer mortality in both women and men [HR = 1.339, 95% confidence interval (CI) = 1.170-1.531, P < 0.001; HR = 1.346, 95% CI = 1.176-1.540, P < 0.001, respectively]. For specific cancer types, low HGS was associated with breast cancer (HR = 1.593, 95% CI = 1.230-2.063, P < 0.001) in women, and lung cancer (HR = 1.369, 95% CI = 1.005-1.866, P = 0.047) and colorectal cancer (HR = 1.399, 95% CI = 1.007-1.944, P = 0.045) in men., Conclusions: On the basis of our sex-specific cut-off points, low HGS was strongly associated with cancer mortalities. These results indicate the usefulness of HGS measurement in routine clinical practice for improving patient assessments, cancer prognosis, and intervention., (© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Objectives: Asymptomatic patients, together with those with mild symptoms of coronavirus disease 2019 (COVID-19), may play an important role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. However, the dynamics of virus shedding during the various phases of the clinical course of COVID-19 remains unclear at this stage., Methods: A total of 18 patients found to be positive for SARS-CoV-2 infection by real-time reverse transcription PCR (RT-PCR) assay and admitted to Chongqing University Central Hospital between 29 January and 5 February 2020 were enrolled into this study. Medical data, pulmonary computed tomographic (CT) scan images and RT-PCR results were periodically collected during the patients' hospital stay. All participants were actively followed up for 2 weeks after discharge., Results: A total of nine (50%) asymptomatic patients and nine (50%) patients with mild symptoms of COVID-19 were identified at admission. Six patients (66.7%) who were asymptomatic at admission developed subjective symptoms during hospitalization and were recategorized as being presymptomatic. The median duration of virus shedding was 11.5, 28 and 31 days for presymptomatic, asymptomatic and mildly symptomatic patients, separately. Seven patients (38.9%) continued to shed virus after hospital discharge. During the convalescent phase, detectable antibodies to SARS-CoV-2 and RNA were simultaneously observed in five patients (27.8%)., Conclusions: Long-term virus shedding was documented in patients with mild symptoms and in asymptomatic patients. Specific antibody production to SARS-CoV-2 may not guarantee virus clearance after discharge. These observations should be considered when making decisions regarding clinical and public health, and when considering strategies for the prevention and control of SARS-CoV-2 infection., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) has been widely spread in the world with a high mortality. Cytokine storm syndrome (CSS) and acute lung injury caused by SARS-CoV-2 infection severely threaten the patients. With the purpose to find effective and low-toxic drugs to mitigate CSS, entecavir and imipenem were identified to reduce TNF-α using a LPS-induced macrophage model from the anti-infective drug library. Entecavir and imipenem efficiently suppressed the release of inflammatory cytokines by partly intervention of NF-κB activity. The acute lung injury was also alleviated and the survival time was prolonged in mice. In addition, entecavir and imipenem inhibited the release of TNF-α and IL-10 in human peripheral blood mononuclear cells (hPBMCs). Collectively, we proposed that entecavir and imipenem might be candidates for the treatment of CSS., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Sarcopenia is a negative predictor for postoperative recovery. This study was performed to evaluate the short-term outcomes of laparoscopic surgery in colorectal cancer patients with sarcopenia., Methods: We conducted a study of patients who underwent curative surgeries for colorectal cancer in two centers from July 2014 to July 2018. In order to reduce selection bias, we conducted a propensity score matching analysis. Preoperative characteristics including age, gender, anemia, body mass index, hypoalbuminemia, America society of anesthesiology scores, epidural anesthesia, operative procedure, stoma, tumor location, and combined resection were incorporated in the model, and produced 58 matched pairs. The third lumbar skeletal muscle mass, handgrip strength, and 6 m usual gait speed were measured to define sarcopenia. Short-term outcomes were compared between the two groups., Results: In a total of 1136 patients, 272 had sarcopenia diagnosed, and 227 were further analyzed in this study. Among them, 108 patients underwent laparoscopic colorectal surgery and 119 underwent open colorectal surgery. In the matched cohort, the clinical characteristics of the two groups were well matched. The laparoscopic group had significantly reduced overall complications (15.5% vs. 36.2%, P = 0.016) and shorter postoperative hospital stays (10.5 vs. 14, P = 0.027). Subgroup analysis of postoperative complications showed that the incidence of surgical complications (P = 0.032) was lower in the laparoscopic group. Hospitalization costs (P = 0.071) and 30-day readmissions (P = 0.215) were similar between the two groups., Conclusion: Laparoscopic surgery for colorectal cancer is a safe and feasible option with better short-term outcomes in patients with sarcopenia.

Two new anthraquinone derivatives, alterporriol Y ( 1 ) and macrosporin 2- O - α -D-glucopyranoside ( 2 ), together with five known analogues ( 3 - 7 ) were isolated from the fungus Stemphylium lycopersici associated with the gorgonian coral Dichotella gemmacea collected from the South China Sea. Their structures were determined on the basis of detailed spectroscopic analysis and comparison with reported data. The absolute configurations were determined by the ECD method. In an in vitro cytotoxic assay, compound 3 and 4 showed potent effects against HCT-116 and MCF-7 cell lines. Compound 4 also exhibited cytotoxicity toward Huh7 stem cell-like cells.

Background: In 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) reached a consensus on sarcopenia (EWGSOP1). In 2018, the EWGSOP met again (EWGSOP2) to update original definition of sarcopenia. This study aimed to investigate the association of sarcopenia and survival and compare the prognostic effects of sarcopenia as defined by EWGSOP1 and EWGSOP2 after gastrectomy., Methods: We conducted a prospective study including patients who underwent curative gastrectomy for gastric cancer from August 2014 to February 2018. The sarcopenia elements, including skeletal muscle index, muscle attenuation, handgrip strength, and gait speed were measured before surgery. Patients were followed up after gastrectomy to gain the actual clinical outcomes., Results: The prevalence of sarcopenia was 17.0% and 18.9% according to the EWGSOP1 and EWGSOP2 respectively. Sarcopenia was independent risk factor for postoperative complications. Compared with EWGSOP1-sarcopenia, EWGSOP2-sarcopenia and had a higher odds ratio (OR) (2.453 vs. 1.550) in multivariate model. Area under the ROC curve of model including EWGSOP2-sarcopenia was larger than that of the model including EWGSOP1-sarcopenia (AUC 0.653 vs. 0.634, P = 0.021). For both of EWGSOP1 and EWGSOP2, sarcopenia was an independent risk factor for overall survival (OS) and disease-free survival (DFS), but EWGSOP2-sarcopenia seemed to have a higher hazard ratio (OS, 1.667 vs. 1.449; DFS, 1.603 vs. 1.563). In addition, severe sarcopenia, as defined by either EWGSOP2 or EWGSOP1, had a strong predictive power (OR 4.909 vs. 3.827) for postoperative complications. Both versions of severe sarcopenia were significantly predictive of OS and DFS in Cox analysis., Conclusion: Sarcopenia at uniform diagnosis standard was an independent risk factor for survival in patients undergoing radical gastrectomy for gastric cancer. Sarcopenia defined by EWGSOP2 criteria better predicts clinical outcomes than that defined by EWGSOP1 criteria in patients with gastric cancer after gastrectomy., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

The principle of sphincter-preserving surgery is to preserve the anal sphincter function under the premise of radical resection. Due to low position of rectal tumor, conventional laparoscopic surgery has difficulties in operating in the deep and narrow pelvis, which may lead to inaccurate tissue dissociation, imprecise positioning of tumor edge, excessive stretch of the anal sphincter complex, and excessive removal of distal rectal mucosa. Moreover, pain from abdominal auxiliary incision has an unavoidable side effect for postoperative recovery. With the help of the Liu's transanal microsurgery system, precision functional sphincter-preserving surgery (PPS) can be successfully performed. PPS tries to preserve left colonic artery and pelvic autonomic nerve in the transabdominal operation. In the part of transanal surgery, measurement, localization and resection of the lower edge of the tumor are conducted under a clear and open visual field with the transparent screw anal dilator. After the rectum is cut off, the specimen is taken out through the anus to avoid abdominal incision. Inserting the intestinal supporter to support the bowel stump, full thickness of bowel stump is then sutured with anal canal by vertical mattress suture. Special transanal tube is placed afterwards without routine prophylactic stoma. PPS can achieve precise tumor resection and sphincter preservation simultaneously.

Scaffold hopping is a frequently-used strategy in the development of non-nucleoside reverse transcriptase inhibitors. Herein, CH(CN)-DAPYs were designed by hopping the cyano-methylene linker of our previous published CH(CN)-DABOs onto the etravirine (ETR). Eighteen CH(CN)-DAPYs were synthesized and evaluated for their anti-HIV activity. Most compounds exhibited promising activity against wild-type (WT) HIV-1. Compounds B4 (EC 50 = 6 nM) and B6 (EC 50 = 8 nM) showed single-digit nanomolar potency against WT HIV-1. Moreover, these two compounds had EC 50 values of 0.06 and 0.08 μM toward the K103N mutant, respectively, which were comparable to the reference efavirenz (EFV) (EC 50 = 0.08 μM). The preliminary structure-activity relationship (SAR) indicated that introducing substitutions on C2 of the 4-cyanophenyl group could improve antiviral activity. Molecular docking predicted that the cyano-methylene linker was positioned into the hydrophobic cavity formed by Y181/Y188 and V179 residues.

Objective: Although there is international consensus regarding the importance of cachexia, no tools exist, to our knowledge, for cachexia screening among patients with cancer. The aim of this study was to evaluate whether patients with cancer and cachexia could be identified using the four most commonly used nutritional screening tools: the Malnutrition Universal Screening Tool (MUST), the Nutritional Risk Screening (NRS)-2002, the Malnutrition Screening Tool (MST), and the Short Nutritional Assessment Questionnaire (SNAQ)., Methods: Clinical data were prospectively collected for patients who underwent elective radical gastrectomy for gastric cancer in two large centers between August 2014 and February 2018. Patients were also screened using the MUST, NRS-2002, MST, and SNAQ tools. The screening results were subsequently compared with the international consensus diagnostic criteria for cancer cachexia., Results: A total of 1001 patients were evaluated, including 363 patients (36.3%) with cancer cachexia. Among the patients "at nutritional risk" based on each tool, the proportions of cachexia were 87.3% for the MUST tool, 84.3% for the MST tool, 76.6% for the NRS-2002 tool, and 54.3% for the SNAQ tool. The MST tool provided the largest area under the curve for identifying cancer cachexia (0.914; P < 0.001)., Conclusion: Among the tools examined, the MST had the greatest ability to detect cancer cachexia among patients with gastric cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Increasing evidence has suggested that sarcopenia is linked with cancer prognosis, but only limited data have focused on the impact of myosteatosis on cancer outcomes. This study evaluates the influence of myosteatosis on postoperative complications and survival in those patients who underwent radical resection of gastric carcinoma., Methods: Patients who underwent elective radical gastrectomy for gastric cancer and had computed tomographic images available were identified from a prospectively collected database between 2008 and 2013. Myosteatosis was diagnosed by the cutoff values obtained from the method of optimum stratification. To obtain 2 well-balanced cohorts for available variables influencing clinical outcomes, the myosteatosis group was matched 1:1 with nonmyosteatosis group by using a propensity score match., Results: Of 973 patients, 584 were matched for analyses. Compared with the nonmyosteatosis group, the myosteatosis group manifested significantly higher severe postoperative complications rates, shorter overall survival, and disease-free survival. Before matching, multivariate analyses identified that myosteatosis was an independent risk factor for severe postoperative complications, and Cox proportions hazards model showed that myosteatosis was an independent predictor for shorter overall survival and disease-free survival. In addition, subgroup analyses of each muscle phenotype showed that patients with both sarcopenia and myosteatosis had a poorer overall survival and disease-free survival than other patients., Conclusion: Myosteatosis in gastric cancer is associated with poor prognosis. Classifying the skeletal muscle into subranges of radio density is a promising strategy to understand the impact of skeletal muscle on unfavorable surgical outcomes in gastric cancer patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The association between sarcopenia and postoperative outcomes in patients who undergo laparoscopic-assisted gastrectomy is unclear. We aimed to determine the predictive value of sarcopenia for adverse postoperative outcomes after laparoscopic-assisted gastrectomy for gastric cancer., Materials and Methods: We prospectively collected the clinical data of patients who underwent elective radical laparoscopic-assisted gastrectomy for gastric cancer in two large centers from August 2014 to October 2017. The third lumbar vertebra skeletal muscle index, handgrip strength, and 6-m usual gait speed were measured to diagnose sarcopenia. Subsequently, we aimed to identify the risk factors for postoperative complications., Results: The study included 313 patients and 37 (11.8%) patients were classified as sarcopenic. Compared with non-sarcopenic patients, sarcopenic patients were significantly older (P < 0.001), had higher nutritional risk screening 2002 scores (P = 0.013), Charlson comorbidity index (CCI) scores (P = 0.033), and neutrophil to lymphocyte ratio (P = 0.004), and lower body mass index (P < 0.001), preoperative serum albumin (P < 0.001), and hemoglobin (P < 0.001). Sarcopenic patients had higher postoperative complication rate (P = 0.002), longer postoperative hospital stays (P = 0.020) and higher total cost of hospitalization (P = 0.001). Multivariate analysis revealed that CCI score ≥1 (odds ratio [OR]: 2.424, 95% confidence interval [CI]: 1.309-4.487; P = 0.005) and sarcopenia (OR: 2.752, 95% CI: 1.274-5.944; P = 0.010) were independent risk factors for short-term postoperative complications., Conclusion: Sarcopenia is an independent clinical predictor of short-term postoperative complications after laparoscopic-assisted gastrectomy., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Three new compounds (9-11) were isolated together with eight known analogues from the fungus Pseudallescheria boydii associated with the South China Sea soft coral Sinularia sandensis. The structures of the new compounds were elucidated on the basis of the spectroscopic analysis, and the absolute configurations including the sulfur stereogenic center of a sulfoxide moiety were determined by comparison of experimental ECD spectra to TDDFT/ECD calculations. Epimeric chiral sulfoxides differing in the absolute configuration of the sulfur chirality center could be efficiently distinguished and assigned by comparing the experimental ECD to those of calculations for the sulfur epimers. In the in vitro biotests for osteoclastogenesis effects, compounds 1, 5, 7, and 10 exhibited a stimulatory activity, while compound 3 displayed an inhibitory activity.

Aim: Mitochondrial dysfunction during aging is a key factor that contributes to sarcopenia. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been increasingly recognized to regulate mitochondrial function. The present study aimed to investigate the role of Nrf2 in the development of frailty and sarcopenia during aging, and to demonstrate whether Nrf2 contributes to the maintenance of muscle mass and function by regulation of mitochondrial biogenesis and dynamics during the aging process., Methods: Young (5-6 months), middle-aged (11-13 months), old (20-24 months) Nrf2-/- (knockout, KO) mice and age-matched wild-type (WT) C57/BL6 mice were used in this study. Physical function of the mice in the 6 groups was assessed by grip strength test, four paw inverted hanging test, rotarod analysis, open field analysis, and treadmill endurance test. Muscle mass was measured by cross-sectional area (CSA) of tibialis anterior muscles and gastrocnemius muscle weight. The frailty status of the 25 old WT mice and 23 old KO mice were assessed based on the mouse frailty phenotype assessment. Expression levels of genes involved in mitochondrial biogenesis (nuclear respiratory factor 1 (Nrf1), peroxisome proliferative activated receptor, gamma, coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (TFAM)) and mitochondrial dynamics (optic atrophy protein 1 (Opa1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and dynamin-related protein 1 (Drp1)) were measured in the skeletal muscle. SDH staining was performed and mitochondrial DNA (mtDNA) copy number was measured. Transmission electron microscopy was used to measure the mitochondria number and morphology., Results: Physical function and muscle mass decreased during aging. The mRNA expression levels of Nrf2 decreased with increasing frailty phenotype scores in the old WT mice. There were minimal differences in the physical function and muscle mass between the WT and KO mice in the young groups, whereas Nrf2 deficiency caused a declined physical function and muscle mass in the middle-aged and old mice, and exacerbated frailty in the old mice. The decreases of the physical function and muscle mass were accompanied by the reduced expression levels of genes involved in mitochondrial biogenesis and dynamics, as well as a reduction of mitochondrial number, mitochondrial content, mtDNA copy number, and an impaired mitochondria morphology in the skeletal muscle., Conclusion: Nrf2 deficiency exacerbated frailty and sarcopenia during aging, at least partially by impairing skeletal muscle mitochondrial biogenesis and dynamics in an age-dependent manner., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to investigate the prevalence of sarcopenia in patients without nutritional risk and the association between sarcopenia and postoperative outcomes after radical gastrectomy in these patients., Method: We conducted a study of non-nutritional risk patients with gastric cancer who underwent gastrectomy from August 2014 to December 2017 in two centers. Nutritional Risk Screening 2002 (NRS 2002) was used to evaluate the nutritional risk. Patients who with NRS 2002 score <3 were classified as having no nutritional risk and were included in the study. Demographic and perioperative data were gathered. Sarcopenia was diagnosed based on the European Working Group on Sarcopenia in Older People criteria. Univariate and multivariate analysis were performed to determine the association between preoperative risk factors and postoperative complications., Results: In all, 545 patients were included, in which the prevalence of sarcopenia and postoperative complications was 7.3% and 21.1%, respectively. Sarcopenia was significantly associated with higher age, lower body mass index, lower handgrip strength, lower usual walking speed, longer postoperative hospital length of stay, and higher costs. Multivariate analysis of prognostic factors revealed that sarcopenia was an independent predictor (odds ratio, 2.330; 95% confidence interval, 1.132-4.796; P = 0.022] for postoperative complications. Male sex, diabetes, and preoperative anemia also were risk factors for postoperative complications., Conclusion: Sarcopenia was a significant independent risk factor for postoperative complications after gastrectomy in patients without nutritional risk. Preoperative assessment and management of sarcopenia should be helpful for improving clinical outcomes for patients without nutritional risk., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A new Keap1-Nrf2 protein-protein interaction (PPI) inhibitor ZJ01 was identified from our compound library by fluorescence polarization assay, surface plasmon resonance, molecular docking and molecular dynamics simulation. ZJ01 could in vitro trigger Nrf2 nuclear translocation, subsequently resulting in increased mRNA levels of Nrf2 target genes HO-1 and NQO1. Meanwhile, ZJ01 suppressed LPS-induced production of ROS and the mRNA levels of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 in H9c2 cardiac cells. Moreover, in an in vivo mouse model of septic cardiomyopathy induced by intraperitoneal injection of lipopolysaccharide, ZJ01 demonstrated a cytoprotective effect, upregulated Nrf2 protein nuclear accumulation, and remarkably suppressed the abovementioned cytokine levels in cardiomyocytes. The results presented herein provided a novel chemotype for the development of direct Keap1-Nrf2 PPI inhibitors and suggested that compound ZJ01 is a promising drug lead for septic cardiomyopathy treatment. ZJ01 was identified as a new Keap1-Nrf2 PPI inhibitor and drug lead for septic cardiomyopathy treatment by in vitro and in vivo experiments.

A new ten-membered macrolide (1) and a new α-pyrone derivative, (-)-annularin C (2), together with 14 known analogs (3-16) were isolated from the AcOEt extract of the fungus Xylaria feejeensis isolated from the South China Sea sponge Stylissa massa. The structures of the new compounds were elucidated by the spectroscopic analysis and by comparison with reported data. The absolute configuration was determined by the optical rotation and ECD experiments. In an in vitro test, compounds 1, 5 and 9 exhibited significant down-regulating activity of osteoclast cell differentiation at 0.5 and 1 μm. This is the first report of the fungus X. feejeensis from a marine sponge and of osteoclastogenesis inhibitory activity for the metabolites of these kinds., (© 2018 Wiley-VHCA AG, Zurich, Switzerland.)

Swinhoeisterols C-F (1-4), four new steroids having a rearranged 6/6/5/7 ring system, were isolated from the Xisha sponge Theonella swinhoei, together with the known analogue swinhoeisterol A (5). Their structures were determined based on spectroscopic analysis, TDDFT-ECD and optical rotation calculations, and biogenetic correlations. In an in vitro assay, compound 1 showed an inhibitory effect on (h)p300 with an IC 50 value of 8.8 μM, whereas compounds 2-4 were not active.