Clinical impact of sarcopenia for overweight or obese patients with colorectal cancer.

BACKGROUND: Sarcopenia, overweight and obesity are all dynamic changes in body composition, which may have a negative effect on the prognosis for patients with colorectal cancer. The aim of this study was to investigate the predictive role of sarcopenia on overweight or obese patients with colorectal cancer. METHODS: We conducted an observative study on the population of overweight or obese patients with colorectal cancer who underwent curative surgeries in two centers between 2015 and 2021. They were grouped by the presence of sarcopenia. Propensity score match analysis was used to balance the baseline of clinicopathologic characteristics of the two groups. Then, the postoperative outcomes between the two groups were compared. Independent risk factors were evaluated for complications using univariate and multivariate analysis. RESULTS: Of 827 patients enrolled, 126 patients were matched for analysis. Patients with sarcopenia had a higher incidence of total complication and medical complications, a higher rate of laparoscopic surgery performed and higher hospitalization costs. Old age (≥65 years, P = 0.012), ASA grade (III, P = 0.008) and sarcopenia (P = 0.036) were independent risk factors for total complications. ASA grade (III, P = 0.002) and sarcopenia (P = 0.017) were independent risk factors for medical complications. CONCLUSIONS: Sarcopenia was prevalent among overweight or obese patients with colorectal cancer and was associated with negative postoperative outcomes. Early recognition of changes in body composition could help surgeons be well prepared for surgical treatment for overweight or obese patients.

Cachexia Versus Sarcopenia in Clinical Characteristics and Prognostic Value After Radical Gastrectomy for Gastric Cancer: A Large-Scale Prospective Study.

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.

Sound field reconstruction using block sparse Bayesian learning equivalent source method.

Nearfield acoustic holography based on the compressed sensing theory can realize the accurate reconstruction of sound fields with fewer measurement points on the premise that an appropriate sparse basis is obtained. However, for different types of sound sources, the appropriate sparse bases are diverse and should be constructed elaborately. In this paper, a block sparse Bayesian learning (SBL) equivalent source method is proposed for realizing the reconstruction of the sound fields radiated by different types of sources, including the spatially sparse sources, the spatially extended sources, and the mixed ones of the above two, without the elaborate construction of the sparse basis. The proposed method constructs a block sparse equivalent source model and promotes a block sparse solution by imposing a structured prior on the equivalent source model and estimating the posterior of the model by using the SBL, which can achieve the accurate reconstruction of the radiated sound fields of different types of sources simply by adjusting the block size. Numerical simulation and experimental results demonstrate the validity and superiority of the proposed method, and the effects of two key parameters, the block size, and sparsity pruning threshold value are investigated through simulations.

Precision functional sphincter-preserving surgery (PPS) for ultralow rectal cancer: a natural orifice specimen extraction (NOSE) surgery technique.

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.

Laparoscopic versus open resection for elderly patients with gastric cancer: a double-center study with propensity score matching method.

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.

Laparoscopic colorectal cancer surgery reduces the adverse impacts of sarcopenia on postoperative outcomes: a propensity score-matched analysis.

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.

NaBr-Induced Production of Brominated Azaphilones and Related Tricyclic Polyketides by the Marine-Derived Fungus Penicillium janthinellum HK1-6.

Cultivation of the mangrove rhizosphere soil-derived fungus Penicillium janthinellum HK1-6 with NaBr led to the isolation of two new brominated azaphilones, penicilones G and H (5, 6), two new tricyclic polyketides, penijanthinones A and B (7, 8), and two known azaphilones, penicilones A and B (1, 2). The planar structures and relative configurations of the new compounds were elucidated using comprehensive spectroscopic methods including 1D and 2D NOE spectra. Their absolute configurations were determined by chemical conversions, TDDFT ECD calculations, and comparisons of their ECD spectra. Interestingly, the NaBr-induced brominated azaphilones (5, 6) had the opposite configuration at C-7 compared to the chloro analogues (3, 4) produced by this fungus cultivated with sea salt. Ester hydrolysis of penicilone B (2) afforded the carboxylic acid side chain 2,4-dimethyldec-2-enoic acid (9), with a 4 S configuration assigned by its specific rotation. Penicilone H (6) showed antibacterial activity with MIC values ranging from 3.13 to 12.5 µg/mL.

Phomopsis liquidambari colonization promotes continuous cropping peanut growth by improving the rhizosphere microenvironment, nutrient uptake and disease incidence.

BACKGROUND: The continuous cropping of peanuts is a primary cause of yield and quality loss. Solutions to this problem should be therefore developed to ensure the sustainability of peanut production. RESULTS: In this study, colonization by the endophytic fungus Phomopsis liquidambari was detected, which led to significantly improved rhizosphere soil microenvironment, enhanced N, P and K assimilation and suppressed incidence of peanut disease. Statistical analysis demonstrated that the yield enhancement was significantly correlated with improvement of the rhizosphere soil microenvironment and the peanut's physiological status by P. liquidambari colonization. In addition, P. liquidambari colonization also significantly improved peanut quality. CONCLUSION: Our results indicate that the practical application of the endophytic fungus P. liquidambari has a strong potential to alleviate the obstacles associated with continuous peanut cropping under field conditions. © 2018 Society of Chemical Industry.

Impact of Visceral Obesity and Sarcopenia on Short-Term Outcomes After Colorectal Cancer Surgery.

BACKGROUND: With the increased prevalence of obesity and sarcopenia, those patients with both visceral obesity and sarcopenia were at higher risk of adverse outcomes. AIM: The aim of this study was to ascertain the combined impact of visceral obesity and sarcopenia on short-term outcomes in patients undergoing colorectal cancer surgery. METHODS: We conducted a prospective study from July 2014 to February 2017. Patients' demographic, clinical characteristics, physical performance, and postoperative short-term outcomes were collected. Patients were classified into four groups according to the presence of sarcopenia or visceral obesity. Clinical variables were compared. Univariate and multivariate analyses evaluating the risk factors for postoperative complications were performed. RESULTS: A total of 376 patients were included; 50.8 and 24.5% of the patients were identified as having "visceral obesity" and "sarcopenia," respectively. Patients with sarcopenia and visceral obesity had the highest incidence of total, surgical, and medical complications. Patients with sarcopenia or/and visceral obesity all had longer hospital stays and higher hospitalization costs. Age ≥ 65 years, visceral obesity, and sarcopenia were independent risk factors for total complications. Rectal cancer and visceral obesity were independent risk factors for surgical complications. Age ≥ 65 years and sarcopenia were independent risk factors for medical complications. Laparoscopy-assisted operation was a protective factor for total and medical complications. CONCLUSION: Patients with both visceral obesity and sarcopenia had a higher complication rate after colorectal cancer surgery. Age ≥ 65 years, visceral obesity, and sarcopenia were independent risk factors for total complications. Laparoscopy-assisted operation was a protective factor.

Sarcopenia: a new predictor of postoperative complications for elderly gastric cancer patients who underwent radical gastrectomy.

BACKGROUND: A geriatric assessment is needed to identify high-risk elderly patients with gastric cancer. However, the current geriatric assessment has been considered to be either time-consuming or subjective. The present study aimed to investigate the predictive effect of sarcopenia on the postoperative complications for elderly patients who underwent radical gastrectomy. MATERIALS AND METHODS: We conducted a prospective study of patients who underwent radical gastrectomy from August 2014 to December 2015. Computed tomography-assessed lumbar skeletal muscle, handgrip strength, and gait speed were measured to define sarcopenia. RESULTS: Sarcopenia was present in 69 of 240 patients (28.8%) and was associated with lower body mass index, lower serum albumin, lower hemoglobin, and higher nutritional risk screening 2002 scores. Postoperative complications significantly increased in the sarcopenic patients (49.3% versus 24.6%, P < 0.001), compared with nonsarcopenic patients. The multivariate analysis demonstrated that sarcopenia (odds ratio: 2.959, 95% CI: 1.629-5.373, P < 0.001) and the Charlson comorbidity index ≥2 (odds ratio: 3.357, 95% CI: 1.144-9.848, P = 0.027) were independent risk factors for postoperative complications. CONCLUSIONS: Sarcopenia, presented as a new geriatric assessment factor, was a strong and independent risk factor for postoperative complications of elderly patients with gastric cancer.

A quantified risk-scoring system and rating model for postsurgical gastroparesis syndrome in gastric cancer patients.

BACKGROUND AND OBJECTIVES: The study aimed to investigate the relationship between obesity and postsurgical gastroparesis syndrome (PGS), and to construct a scoring system and a risk model to identify patients at high risk. METHODS: A total of 634 patients were retrospectively analyzed. Clinical characteristics were evaluated via receiver operating characteristic (ROC) curve analysis. Logistic analysis was performed to determine the independent predictive indicators of PGS. A scoring system consisting of these indicators and a risk-rating model were constructed and evaluated via ROC curve analysis. RESULTS: Based on the ROC curves, the visceral fat area (VFA) cutoff value for PGS was 94.00. Logistic analysis showed that visceral obesity (VFA ≥ 94.00 cm2 ), the reconstruction technique, and tumor size were independent prognostic factors for PGS. The scoring system could predict PGS reliably with a high area under the ROC curve ([AUC] = 0.769). A high-risk rating had a high AUC (AUC I = 0.56, AUC II = 0.65, and AUC III = 0.77), indicating that the risk-rating model could effectively screen patients at high risk of PGS. CONCLUSIONS: Visceral obesity defined by VFA effectively predicted PGS. Our scoring system may be a reliable instrument for identifying patients most at risk of PGS.

The Endophytic Fungus Phomopsis liquidambari Increases Nodulation and N2 Fixation in Arachis hypogaea by Enhancing Hydrogen Peroxide and Nitric Oxide Signalling.

The continuous cropping obstacles in monoculture fields are a major production constraint for peanuts. Application of the endophytic fungus Phomopsis liquidambari has increased peanut yields, and nodulation and N2 fixation increases have been considered as important factors for P. liquidambari infection-improved peanut yield. However, the mechanisms involved in this process remain unknown. This work showed that compared with only Bradyrhizobium inoculation, co-inoculation with P. liquidambari significantly elevated endogenous H2O2 and NO levels in peanut roots. Pre-treatment of seedlings with specific scavengers of H2O2 (CAT) and NO (cPTIO) blocked P. liquidambari-induced nodulation and N2 fixation. CAT not only suppressed the P. liquidambari-induced nodulation and N2 fixation, but also suppressed the enhanced H2O2 and NO generation. Nevertheless, the cPTIO did not significantly inhibit the induced H2O2 biosynthesis, implying that H2O2 acted upstream of NO production. These results were confirmed by observations that exogenous H2O2 and sodium nitroprusside (SNP) reversed the inhibition of P. liquidambari-increased nodulation and N2 fixation by the specific scavengers. The transcriptional activities of the symbiosis-related genes SymRK and CCaMK of peanut-Bradyrhizobium interactions also increased significantly in response to P. liquidambari, H2O2 and SNP treatments. The pot experiment further confirmed that the P. liquidambari infection-enhanced H2O2 and NO signalling pathways were significantly related to the increase in peanut nodulation and N2 fixation. This is the first report that endophytic fungus P. liquidambari can increase peanut-Bradyrhizobium interactions via enhanced H2O2/NO-dependent signalling crosstalk, which is conducive to the alleviation of continuous cropping obstacles via an increase in nodulation and N2 fixation.

Penicilones A-D, Anti-MRSA Azaphilones from the Marine-Derived Fungus Penicillium janthinellum HK1-6.

Four new azaphilones, penicilones A-D (1-4), were isolated from the mangrove rhizosphere soil-derived fungus Penicillium janthinellum HK1-6. Their planar structures and absolute configurations were determined by extensive analysis of NMR spectroscopic data, ECD spectra, the modified Mosher's method, and chemical conversions. Interestingly, 1 and 2 had the opposite configuration at C-7 compared to the closely related chloro analogues 3 and 4. Ester hydrolysis of 2 and 4 afforded their parental azaphilones, named penicilones E (5) and F (6). Compounds 1-6 were evaluated for their antibacterial activities in vitro. Penicilones B-D (2-4) showed potent anti-MRSA (Staphylococcus aureus ATCC 43300, ATCC 33591) activities with MIC values ranging from 3.13 to 6.25 µg/mL.

Establishment and validation of novel nomograms to predict muscle quality in colorectal cancer patients.

OBJECTIVES: The skeletal muscle mass index and skeletal muscle radiodensity have promise as specific diagnostic indicators for muscle quality. However, the difficulties in measuring low skeletal muscle mass index and low skeletal muscle radiodensity limit their use in routine clinical practice, impeding early screening and diagnosis. The objective of this study is to develop a nomogram that incorporates preoperative factors for predicting low skeletal muscle mass index and low skeletal muscle radiodensity. METHODS: A total of 1692 colorectal cancer patients between 2015 and 2021 were included. The patients were randomly divided into a training cohort (n = 1353) and a validation cohort (n = 339). Nomogram models were calibrated using the area under the curve, calibration curves, and the Hosmer-Lemeshow test to assess their predictive ability. Finally, a decision curve was applied to assess the clinical usefulness. RESULTS: In a prediction model for low skeletal muscle mass index, age, body mass index, and grip strength were incorporated as variables. For low skeletal muscle radiodensity, age, sex, body mass index, serum hemoglobin level, and grip strength were included as predictors. In the training cohort, the area under the curve value for low skeletal muscle mass index was 0.750 (95% CI, 0.726-0.773), whereas for low skeletal muscle radiodensity, it was 0.763 (95% CI, 0.739-0.785). The Hosmer-Lemeshow test confirmed that both models fit well in both cohorts. Decision curve analysis was applied to assess the clinical usefulness of the model. CONCLUSIONS: The incorporation of preoperative factors into the nomogram-based prediction model represents a significant advancement in the muscle quality assessment. Its implementation has the potential to early screen patients at risk of low skeletal muscle mass index and low skeletal muscle radiodensity.

Characteristics and prognostic impact of cancer cachexia defined by the Asian Working Group for Cachexia consensus in patients with curable gastric cancer.

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.

Muscle attenuation, not skeletal muscle index, is an independent prognostic factor for survival in gastric cancer patients with overweight and obesity.

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/m2. 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.

Transcriptome profiling of fast/glycolytic and slow/oxidative muscle fibers in aging and obesity.

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.

Activation of free fatty acid receptors, FFAR1 and FFAR4, ameliorates ulcerative colitis by promote fatty acid metabolism and mediate macrophage polarization.

OBJECTIVE: To investigate the mechanism of action of fatty acid receptors, FFAR1 and FFAR4, on ulcerative colitis (UC) through fatty acid metabolism and macrophage polarization. METHODS: Dextran sulfate sodium (DSS)-induced mouse model of UC mice was used to evaluate the efficacy of FFAR1 (GW9508) and FFAR4 (GSK137647) agonists by analyzing body weight, colon length, disease activity index (DAI), and histological scores. Real-time PCR and immunofluorescence analysis were performed to quantify the levels of fatty acid metabolizing enzymes and macrophage makers. FFA-induced lipid accumulation in RAW264.7 cells was visualized by Oil Red O staining analysis, and cells were collected to detect macrophage polarization by flow cytometry. RESULTS: The combination of GW9508 and GSK137647 significantly improved DSS-induced UC symptoms, caused recovery in colon length, and decreased histological injury. GW9508 + GSK137647 treatment upregulated the expressions of CD206, lipid oxidation enzyme (CPT-1α) and anti-inflammatory cytokines (IL-4, IL-10, IL-13) but downregulated those of CD86, lipogenic enzymes (ACC1, FASN, SCD1), and pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α). Combining the two agonists decreased FFA-induced lipid accumulation and increased CD206 expression in cell-based experiments. CONCLUSION: Activated FFAR1 and FFAR4 ameliorates DSS-induced UC by promoting fatty acid metabolism to reduce lipid accumulation and mediate M2 macrophage polarization.

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

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

Sarcopenia and malignancies: epidemiology, clinical classification and implications.

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.