Cellular and circuit architecture of the lateral septum for reward processing.

The lateral septum (LS) is composed of heterogeneous cell types that are important for various motivated behaviors. However, the transcriptional profiles, spatial arrangement, function, and connectivity of these cell types have not been systematically studied. Using single-nucleus RNA sequencing, we delineated diverse genetically defined cell types in the LS that play distinct roles in reward processing. Notably, we found that estrogen receptor 1 (Esr1)-expressing neurons in the ventral LS (LSEsr1) are key drivers of reward seeking via projections to the ventral tegmental area, and these neurons play an essential role in methamphetamine (METH) reward and METH-seeking behavior. Extended exposure to METH increases the excitability of LSEsr1 neurons by upregulating hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, thereby contributing to METH-induced locomotor sensitization. These insights not only elucidate the intricate molecular, circuit, and functional architecture of the septal region in reward processing but also reveal a neural pathway critical for METH reward and behavioral sensitization.

The potential of machine learning models to identify malnutrition diagnosed by GLIM combined with NRS-2002 in colorectal cancer patients without weight loss information.

BACKGROUND & AIMS: The key step of the Global Leadership Initiative on Malnutrition (GLIM) is nutritional risk screening, while the most appropriate screening tool for colorectal cancer (CRC) patients is yet unknown. The GLIM diagnosis relies on weight loss information, and bias or even failure to recall patients' historical weight can cause misestimates of malnutrition. We aimed to compare the suitability of several screening tools in GLIM diagnosis, and establish machine learning (ML) models to predict malnutrition in CRC patients without weight loss information. METHODS: This multicenter cohort study enrolled 4487 CRC patients. The capability of GLIM diagnoses combined with four screening tools in predicting survival probability was compared by Kaplan-Meier curves, and the most accurate one was selected as the malnutrition reference standard. Participants were randomly assigned to a training cohort (n = 3365) and a validation cohort (n = 1122). Several ML approaches were adopted to establish models for predicting malnutrition without weight loss data. We estimated feature importance and reserved the top 30% of variables for retraining simplified models. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were calculated to assess and compare model performance. RESULTS: NRS-2002 was the most suitable screening tool for GLIM diagnosis in CRC patients, with the highest hazard ratio (1.59; 95% CI, 1.43-1.77). A total of 2076 (46.3%) patients were malnourished diagnosed by GLIM combined with NRS-2002. The simplified random forest (RF) model outperformed other models with an AUC of 0.830 (95% CI, 0.805-0.854), and accuracy, sensitivity and specificity were 0.775, 0.835 and 0.742, respectively. We deployed an online application based on the simplified RF model to accurately estimate malnutrition probability in CRC patients without weight loss information (https://zzuwtt1998.shinyapps.io/dynnomapp/). CONCLUSIONS: Nutrition Risk Screening 2002 was the optimal initial nutritional risk screening tool in the GLIM process. The RF model outperformed other models, and an online prediction tool was developed to properly identify patients at high risk of malnutrition.

Integrated neutrophil-to-lymphocyte ratio and handgrip strength better predict survival in patients with cancer cachexia.

OBJECTIVES: Systemic inflammation and skeletal muscle strength play crucial roles in the development and progression of cancer cachexia. In this study we aimed to evaluate the combined prognostic value of neutrophil-to-lymphocyte ratio (NLR) and handgrip strength (HGS) for survival in patients with cancer cachexia. METHODS: This multicenter cohort study involved 1826 patients with cancer cachexia. The NLR-HGS (NH) index was defined as the ratio of neutrophil-to-lymphocyte ratio to handgrip strength. Harrell's C index and receiver operating characteristic (ROC) curve analysis were used to assess the prognosis of NH. Kaplan-Meier analysis and Cox regression models were used to evaluate the association of NH with all-cause mortality. RESULTS: Based on the optimal stratification, 380 women (NH > 0.14) and 249 men (NH > 0.19) were classified as having high NH. NH has shown greater predictive value compared to other indicators in predicting the survival of patients with cancer cachexia according to the 1-, 3-, and 5-y ROC analysis and Harrell's C index calculation. Multivariate survival analysis showed that higher NH was independently associated with an increased risk of death (hazard ratio = 1.654, 95% confidence interval = 1.389-1.969). CONCLUSION: This study demonstrates that the NH index, in combination with NLR and HGS, is an effective predictor of the prognosis of patients with cancer cachexia. It can offer effective prognosis stratification and guidance for their treatment.

Early enteral nutrition versus early supplemental parenteral nutrition in patients undergoing major abdominal surgery: a secondary analysis of 2 randomized clinical trials.

BACKGROUND: The effect of early isoenergetic feeding routes [early enteral nutrition (E-EN) or early supplemental parenteral nutrition (E-SPN)] on the outcome of patients undergoing major abdominal surgery is controversial. OBJECTIVES: The aim of this study was to investigate the impact of early isoenergetic EN compared with early isoenergetic SPN on nosocomial infections in patients undergoing major abdominal surgery. METHODS: This study is a secondary, post hoc analysis of data from 2 open-label randomized clinical trials. Participants were recruited from the general surgery department of 11 academic hospitals in China undergoing major abdominal surgery and with Nutritional Risk Screening 2002 score ≥3. All eligible patients were categorized into 2 groups based on their achievement of the 100% energy target on postoperative day (POD) 3: the E-EN group (n = 199) and the E-SPN group (n = 115). The primary outcome was the incidence of nosocomial infections between POD 3 and hospital discharge. RESULTS: In total, 314 patients [mean (SD) age, 59.2 (11.4) y; 113 (36.0%) females] were included. Patients in the E-EN group showed no significant difference in nosocomial infections compared with those in the E-SPN group {17/199 [8.5%] compared with 10/115 [8.7%], risk difference, 0.2% [95% confidence interval (CI): -6.3, 6.6]}. The hematological nutritional status of the E-EN group showed a significant improvement at discharge compared with the E-SPN group (albumin: 38.0 ± 6.0 g/L compared with 35.5 ± 7.6 g/L; mean difference, -2.5 g/L; 95% CI: -4.0, -1.0 g/L; prealbumin: 200.0 ± 8.0 mg/L compared with 158.4 ± 38.1 mg/L; mean difference, -41.6 mg/L; 95% CI: -41.7, -36.1 mg/L). Other indicators were comparable between groups. CONCLUSION: E-EN compared with isoenergetic SPN may not be associated with a reduced rate of nosocomial infection in patients undergoing major abdominal surgery, but may be associated with improved hematological nutritional status. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov as NCT03115957 (https://clinicaltrials.gov/ct2/show/NCT03115957) and NCT03117348 (https://clinicaltrials.gov/ct2/show/NCT03117348).

Systemic inflammation and insulin resistance-related indicator predicts poor outcome in patients with cancer cachexia.

BACKGROUND: The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia. METHODS: In this study, our prospective multicenter cohort included 1411 patients with cancer cachexia (mean age 59.45 ± 11.38, 63.3% male), which was a combined analysis of multiple cancer types. We randomly selected 30% of the patients for the internal test cohort (mean age 58.90 ± 11.22% 61.4% male). Additionally, we included 307 patients with cancer cachexia in the external validation cohort (mean age 61.16 ± 11, 58.5% male). Receiver operating characteristic (ROC) and calibration curves were performed to investigate the prognostic value of CTI. The prognostic value of the CTI was also investigated performing univariate and multivariate survival analyses. RESULTS: The survival curve indicated that the CTI showed a significant prognostic value in the total, internal, and external validation cohorts. Prognostic ROC curves and calibration curves revealed that the CTI showed good consistency in predicting the survival of patients with cancer cachexia. Multivariate survival analysis showed that an elevated CTI increased the risk of death by 22% (total cohort, 95% confidence interval [CI] = 1.13-1.33), 34% (internal test cohort, 95%CI = 1.11-1.62), and 35% (external validation cohort, 95%CI = 1.14-1.59) for each increase in the standard deviation of CTI. High CTI reliably predicted shorter survival (total cohort, hazard ratio [HR] = 1.45, 95%CI = 1.22-1.71; internal test cohort, HR = 1.62, 95%CI = 1.12-2.36; external validation cohort, HR = 1.61, 95%CI = 1.15-2.26). High CTI significantly predicted shorter survival in different tumor subgroups, such as esophageal [HR = 2.11, 95%CI = 1.05-4.21] and colorectal cancer [HR = 2.29, 95%CI = 1.42-3.71]. The mediating effects analysis found that the mediating proportions of PGSGA, ECOG PS, and EORTC QLQ-C30 on the direct effects of CTI were 21.72%, 19.63%, and 11.61%, respectively We found that there was a significant positive correlation between the CTI and 90-day [HR = 2.48, 95%CI = 1.52-4.14] and 180-day mortality [HR = 1.77,95%CI = 1.24-2.55] in patients with cancer cachexia. CONCLUSION: The CTI can predict the short- and long-term survival of patients with cancer cachexia and provide a useful prognostic tool for clinical practice.

Whole-protein enteral nutrition formula supplementation reduces Escherichia and improves intestinal barrier function in HIV-infected immunological nonresponders.

People living with human immunodeficiency virus (PLWH) have persistent malnutrition, intestinal barrier dysfunction, and gut microbial imbalance. The interplay between gut microbiota and nutrients is involved in the immune reconstitution of PLWH. To evaluate the effects of whole-protein enteral nutrition formula supplementation on T-cell levels, intestinal barrier function, nutritional status, and gut microbiota composition in human immunodeficiency virus (HIV)-infected immunological nonresponders (INRs) who failed to normalize CD4+ T-cell counts, with a number <350 cells/µL, a pilot study was carried out in 13 HIV-infected INRs undergoing antiretroviral therapy who received a 3-month phase supplementation of 200 mL/200 kcal/45 g whole-protein enteral nutrition formula once daily. Our primary endpoint was increased CD4+ T-cell counts. Secondary outcome parameters were changes in intestinal barrier function, nutritional status, and gut microbiota composition. We showed that CD4+ T-cell counts of HIV-infected INRs increased significantly after the 3-month supplementation. Dietary supplementation for 3 months improved the intestinal barrier function and nutritional status of HIV-infected INRs. Furthermore, the enteral nutrition formula significantly decreased the relative abundance of Escherichia at the genus level and increased the alpha diversity of gut microbiota in HIV-infected INRs. The findings demonstrated that the whole-protein enteral nutrition formula aids in reducing Escherichia and improving intestinal barrier function in HIV-infected INRs. This study provides insight into the role of nutrients in the improvement of immune reconstitution in HIV-infected INRs. This study is registered in the Chinese Clinical Trial Registry (Document No. ChiCTR2000037839; http://www.chictr.org.cn/index.aspx).

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

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

Prognostic value of systemic inflammation and for patients with colorectal cancer cachexia.

BACKGROUND: The development and progression of cancer cachexia are connected to systemic inflammation and physical performance. However, few relevant studies have reported the survival outcomes prediction of systemic inflammation and physical performance in patients with colorectal cancer (CRC) cachexia. This study investigated the prognostic prediction value of systemic inflammation and performance status in patients with CRC cachexia. METHODS: This multicentre cohort study prospectively collected 905 patients with CRC (58.3% males, 59.3 ± 11.5 years old). Cancer cachexia was diagnosed according to the 2011 Fearon Cachexia Diagnostic Consensus. The prognostic value of systematic inflammatory indicators was determined using the area under the curve, concordance index, and multivariate survival analysis. Performance status was evaluated with Eastern Coopertive Oncology Group performance score (ECOG-PS). Survival data were analysed using univariate and multivariate Cox regression analyses. RESULTS: The area under the curve, concordance index and survival analysis showed that C-reactive protein (CRP), lymphocyte to CRP ratio (LCR) and CRP to albumin ratio (CAR) were more stable and consistent with the survival of patients with CRC, both in non-cachexia and cachexia populations. Among patients with CRC cachexia, high inflammation [low LCR, hazard ratio (HR) 95% confidence interval (95% CI) = 3.33 (2.08-5.32); high CAR, HR (95% CI) = 2.92 (1.88-4.55); high CRP, HR (95% CI) = 3.12 (2.08-4.67)] indicated a worse prognosis, compared with non-cachexia patients [low LCR, HR (95% CI) = 2.28 (1.65-3.16); high CAR, HR (95% CI) = 2.36 (1.71-3.25); high CRP, HR (95% CI) = 2.58 (1.85-3.60)]. Similarly, among patients with CRC cachexia, high PS [ECOG-PS 2, HR (95% CI) = 1.61 (1.04-2.50); ECOG-PS 3/4, HR (95% CI) = 2.91 (1.69-5.00]) indicated a worse prognosis, compared with patients with CRC without cachexia [ECOG-PS 2, HR (95% CI) = 1.28 (0.90-1.81); ECOG-PS 3/4, HR (95% CI) = 2.41 (1.32-4.39]). Patients with CRC cachexia with an ECOG-PS score of 2 or 3-4 and a high inflammation had a shorter median survival time, compared with patients with an ECOG-PS score of 0/1 and a low inflammation. CONCLUSIONS: The systemic inflammatory markers LCR, CAR and CRP have stable prognostic values in patients with CRC. The ECOG-PS may be an independent risk factor for CRC. Combined evaluation of systemic inflammation and ECOG-PS in patients with CRC cachexia could provide a simple survival prediction.

Robust double-network polyvinyl alcohol-polypyrrole hydrogels as high-performance electrodes for flexible supercapacitors.

The growing demands of flexible and wearable electronic devices boost the rapid development of flexible supercapacitors (FSCs). Conductive hydrogels are considered to be one type of promising electrode materials for FSCs due to their good processability and electrochemical properties. However, the poor mechanical properties of conductive hydrogels hinder their practical applications. Building robust cross-linked network structures is a feasible way to enhance their mechanical properties. Herein, the double-network polyvinyl alcohol (PVA)-polypyrrole (PPy) conductive hydrogels are synthesized by the freeze-thaw and in-situ polymerization method. The double-network structure not only enhances mechanical properties of the hydrogels, but also promotes their electrolyte ion transport. The maximum elongation at break of the optimized PVA-PPy hydrogels can reach 156.4%, and the specific capacitance is 1718.7 mF cm-2 at 0.5 mA cm-2. Furthermore, the energy densities of the symmetrical PVA-PPy FSCs are 46.7 and 13.3 µWh cm-2 at power densities of 200.0 and 2000.0 µW cm-2. Such excellent electrochemical performances and mechanical properties make the synthesized PVA-PPy hydrogels a promising candidate for FSCs.

Effect of early achievement of energy target by different nutritional support strategies on nosocomial infections in patients undergoing major abdominal surgery: a secondary analysis of two randomized clinical trials.

BACKGROUND: The effect of early achievement of energy targets (EAETs) using different nutritional support strategies in patients undergoing major abdominal surgery is unclear. This study determined the impact of EAETs on the incidence of nosocomial infections in patients undergoing major abdominal surgery. METHODS: This was a secondary analysis of two open-label randomized clinical trials. Patients from the general surgery department of 11 academic hospitals in China undergoing major abdominal surgery and at nutritional risk (Nutritional risk screening 2002≥3) were divided into two groups based on whether they met the 70% energy targets, the EAET (521 EAET and non-achievement of energy target (114 NAET) groups. The primary outcome was the incidence of nosocomial infections between postoperative day 3 and discharge, and the secondary outcomes were actual energy and protein intake, postoperative noninfectious complications, intensive care unit admission, mechanical ventilation, and hospital stay. RESULTS: Overall, 635 patients [mean (SD) age, 59.5 (11.3) years] were included. The EAET group received more mean energy between days 3 and 7 than the NAET group (22.7±5.0 vs. 15.1±4.8 kcal/kg/d; P <0.001). The EAET group had significantly fewer nosocomial infections than the NAET group [46/521(8.8%) vs. 21/114(18.4%); risk difference, 9.6%; 95% CI, 2.1-17.1%; P =0.004]. A significant difference was found in the mean (SD) number of noninfectious complications between the EAET and NAET groups [121/521(23.2%) vs. 38/114(33.3%); risk difference, 10.1%; 95% CI, 0.7-19.5%; P =0.024]. The nutritional status of the EAET group was significantly improved at discharge compared with the NAET group ( P <0.001), and other indicators were comparable between groups. CONCLUSION: EAETs was associated with fewer nosocomial infections and improved clinical outcomes, regardless of the nutritional support strategy (early enteral nutrition alone or combined with early supplemental parenteral nutrition).

AIWW: a new nutrition-screening tool for the oncologic population.

Malnutrition is a common comorbidity among patients with cancer. However, no nutrition-screening tool has been recognized in this population. A quick and easy screening tool for nutrition with high sensitivity and easy-to-use is needed. Based on the previous 25 nutrition-screening tools, the Delphi method was made by the members of the Chinese Society of Nutritional Oncology to choose the most useful item from each category. According to these results, we built a nutrition-screening tool named age, intake, weight, and walking (AIWW). Malnutrition was defined based on the scored patient-generated subjective global assessment (PG-SGA). Concurrent validity was evaluated using the Kendall tau coefficient and kappa consistency between the malnutrition risks of AIWW, nutritional risk screening 2002 (NRS-2002), and malnutrition screening tool (MST). Clinical benefit was calculated by the decision curve analysis (DCA), integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). A total of 11,360 patients (male, n=6,024 (53.0%) were included in the final study cohort, and 6,363 patients had malnutrition based on PG-SGA. Based on AIWW, NRS-2002, and MST, 7,545, 3,469, and 1,840 patients were at risk of malnutrition, respectively. The sensitivities of AIWW, NRS-2002, and MST risks were 0.910, 0.531, and 0.285, and the specificities were 0.768, 0.946, and 0.975. The Kendall tau coefficients of AIWW, NRS-2002, and MST risks were 0.588, 0.501, and 0.326, respectively. The area under the curve of AIWW, NRS-2002, and MST risks were 0.785, 0.739, and 0.630, respectively. The IDI, cNRI, and DCA showed that AIWW is non-inferior to NRS-2002 (IDI: 0.002 (-0.009, 0.013), cNRI: -0.015 (-0.049, 0.020)). AIWW scores can also predict the survival of patients with cancer. The missed diagnosis rates of AIWW, NRS-2002, and MST were 0.09%, 49.0%, and 73.2%, respectively. AIWW showed a better nutrition-screening effect than NRS-2002 and MST for patients with cancer and could be recommended as an alternative nutrition-screening tool for this population.

The prognostic value of the combination of body composition and systemic inflammation in patients with cancer cachexia.

BACKGROUND: Changes in body composition and systemic inflammation are important characteristics of cancer cachexia. This multi-centre retrospective study aimed to explore the prognostic value of the combination of body composition and systemic inflammation in patients with cancer cachexia. METHODS: The modified advanced lung cancer inflammation index (mALI), which combines body composition and systemic inflammation, was defined as appendicular skeletal muscle index (ASMI) × serum albumin/neutrophil-lymphocyte ratio. The ASMI was estimated according to a previously validated anthropometric equation. Restricted cubic splines were used to evaluate the relationship between mALI and all-cause mortality in patients with cancer cachexia. Kaplan-Meier analysis and Cox proportional hazard regression analysis were used to evaluate the prognostic value of mALI in cancer cachexia. A receiver operator characteristic curve was used to compare the effectiveness of mALI and nutritional inflammatory indicators in predicting all-cause mortality in patients with cancer cachexia. RESULTS: A total of 2438 patients with cancer cachexia were enrolled, including 1431 males and 1007 females. The sex-specific optimal cut-off values of mALI for males and females were 7.12 and 6.52, respectively. There was a non-linear relationship between mALI and all-cause mortality in patients with cancer cachexia. Low mALI was significantly associated with poor nutritional status, high tumour burden, and high inflammation. Patients with low mALI had significantly lower overall survival (OS) than those with high mALI (39.5% vs. 65.5%, P < 0.001). In the male population, OS was significantly lower in the low mALI group than in the high group (34.3% vs. 59.2%, P < 0.001). Similar results were also observed in the female population (46.3% vs. 75.0%, P < 0.001). mALI was an independent prognostic factor for patients with cancer cachexia (hazard ratio [HR] = 0.974, 95% confidence interval [CI] = 0.959-0.990, P = 0.001). For every standard deviation [SD] increase in mALI, the risk of poor prognosis for patients with cancer cachexia was reduced by 2.9% (HR = 0.971, 95%CI = 0.943-0.964, P < 0.001) in males and 8.9% (HR = 0.911, 95%CI = 0.893-0.930, P < 0.001) in females. mALI is an effective complement to the traditional Tumour, Lymph Nodes, Metastasis (TNM) staging system for prognosis evaluation and a promising nutritional inflammatory indicator with a better prognostic effect than the most commonly used clinical nutritional inflammatory indicators. CONCLUSIONS: Low mALI is associated with poor survival in both male and female patients with cancer cachexia and is a practical and valuable prognostic assessment tool.

The combination of hand grip strength and modified Glasgow prognostic score predicts clinical outcomes in patients with liver cancer.

Purpose: Previous studies have shown that both hand grip strength (HGS) and the modified Glasgow Prognostic Score (mGPS) are associated with poor clinical outcomes in patients with liver cancer. In spite of this, no relevant studies have been conducted to determine whether the combination of HGS and mGPS can predict the prognosis of patients with liver cancer. Accordingly, this study sought to explore this possibility. Methods: This was a multicenter study of patients with liver cancer. Based on the optimal HGS cutoff value for each sex, we determined the HGS cutoff values. The patients were divided into high and low HGS groups based on their HGS scores. An mGPS of 0 was defined as low mGPS, whereas scores higher than 0 were defined as high mGPS. The patients were combined into HGS-mGPS groups for the prediction of survival. Survival analysis was performed using Kaplan-Meier curves. A Cox regression model was designed and adjusted for confounders. To evaluate the nomogram model, receiver operating characteristic curves and calibration curves were used. Results: A total of 504 patients were enrolled in this study. Of these, 386 (76.6%) were men (mean [SD] age, 56.63 [12.06] years). Multivariate analysis revealed that patients with low HGS and high mGPS had a higher risk of death than those with neither low HGS nor high mGPS (hazard ratio [HR],1.50; 95% confidence interval [CI],1.14-1.98; p = 0.001 and HR, 1.55; 95% CI, 1.14-2.12, p = 0.001 respectively). Patients with both low HGS and high mGPS had 2.35-fold increased risk of death (HR, 2.35; 95% CI, 1.52-3.63; p < 0.001). The area under the curve of HGS-mGPS was 0.623. The calibration curve demonstrated the validity of the HGS-mGPS nomogram model for predicting the survival of patients with liver cancer. Conclusion: A combination of low HGS and high mGPS is associated with poor prognosis in patients with liver cancer. The combination of HGS and mGPS can predict the prognosis of liver cancer more accurately than HGS or mGPS alone. The nomogram model developed in this study can effectively predict the survival outcomes of liver cancer.

Comprehensive prognostic effects of systemic inflammation and Insulin resistance in women with breast cancer with different BMI: a prospective multicenter cohort.

To investigate the prognostic value of systemic inflammation and insulin resistance in women with breast cancer with different body mass index (BMI). This multicenter, prospective study included 514 women with breast cancer. Multivariate survival analysis showed that patients with high C-reactive protein (CRP), high CRP to albumin ratio (CAR), high lymphocyte to CRP ratio (LCR), high low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (LHR), and high triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-c) were significantly associated with worse prognosis. The mortality rate of patients with both high CAR and high LHR or both low LCR and high LHR were 3.91-fold or 3.89-fold higher than patients with both low CAR and low LHR or both high LCR and low LHR, respectively. Furthermore, the combination of LCR and LHR significantly predicted survival in patients within the high BMI group. The CRP, CAR, LCR, LHR, and TG/HDL-c were associated with poor survival in women with breast cancer. The combination of CAR and LHR or LCR and LHR could better predict the prognostic outcomes of women with breast cancer, while the combination of LCR and LHR could better predict the prognosis of those patients with overweight or obese patients.

In silico development and in vitro validation of a novel five-gene signature for prognostic prediction in colon cancer.

Colon cancer is one of the most common cancers in digestive system, and its prognosis remains unsatisfactory. Therefore, this study aimed to identify gene signatures that could effectively predict the prognosis of colon cancer patients by examining the data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. LASSO-Cox regression analysis generated a five-gene signature (DCBLD2, RAB11FIP1, CTLA4, HOXC6 and KRT6A) that was associated with patient survival in the TCGA cohort. The prognostic value of this gene signature was further validated in two independent GEO datasets. GO enrichment revealed that the function of this gene signature was mainly associated with extracellular matrix organization, collagen-containing extracellular matrix, and extracellular matrix structural constituent. Moreover, a nomogram was established to facilitate the clinical application of this signature. The relationships among the gene signature, mutational landscape and immune infiltration cells were also investigated. Importantly, this gene signature also reliably predicted the overall survival in IMvigor210 anti-PD-L1 cohort. In addition to the bioinformatics study, we also conducted a series of in vitro experiments to demonstrate the effect of the signature genes on the proliferation, migration, and invasion of colon cancer cells. Collectively, our data demonstrated that this five-gene signature might serve as a promising prognostic biomarker and shed light on the development of personalized treatment in colon cancer patients.

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

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

Handgrip weakness, systemic inflammation indicators, and overall survival in lung cancer patients with well performance status: A large multicenter observational study.

BACKGROUND: Systemic inflammation and handgrip weakness have been used to predict mortality in many cancers. The purpose of current study was to evaluate the association of co-occurrence of inflammation indicators and handgrip weakness with overall survival (OS) of lung cancer (LC) patients with good performance status. METHODS: The cutoff points for handgrip strength (HGS) and the four inflammation indicators were calculated using Maxstat. The time-dependent receiver operating characteristic curve and C-index were used to select optimal inflammation indicator for predicting OS of LC patients. The Cox proportional hazard regression model was used to calculate the hazard ratio (HR) of mortality. Kaplan-Meier curves were constructed to evaluate the association of indicators and the OS of LC patients. RESULTS: Among the 1951 patients, the mean ± standard deviation (SD) age was 60.6 ± 9.9 years, and 1300 (66.6%) patients were male. In patients with good performance status (PS), handgrip weakness (HR, 1.49; 95% confidence interval [95% CI], 1.30-1.70, p < 0.001) and low advanced lung cancer inflammation index (ALI) (HR, 2.05; 95%CI, 1.79-2.34, p < 0.001), high systemic immune-inflammation index (SII) (HR, 1.91; 95%CI, 1.66-2.19, p < 0.001), high platelet: lymphocyte ratio (PLR) (HR, 1.60; 95%CI, 1.40-1.82, p < 0.001), or high neutrophil: lymphocyte ratio (NLR) (HR, 2.01; 95%CI, 1.76-2.30, p < 0.001) were associated with increased mortality risk of LC patients. ALI had better C-index (0.624) and time-AUC in the prediction of OS in LC patients with good PS than other three combinations. The co-occurrence of handgrip weakness and low ALI more than doubled the risk of death in LC with good PS (HR, 2.44; 95% CI, 2.06-2.89, p < 0.001). CONCLUSION: In LC patients who have good PS, patients with combined handgrip weakness and low ALI have the worst prognosis. THE TRIAL REGISTRATION NUMBER: ChiCTR1800020329.

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

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

Association of systemic inflammation and low performance status with reduced survival outcome in older adults with cancer.

BACKGROUND: Inflammation is involved in the progression and prognosis of cancer because it can affect the physical status and prognosis of patients. Among numerous systemic inflammatory markers, the optimal prognostic indicator of older adults with cancer is still unclear. We aimed to identify an ideal inflammatory immune marker in older adults with cancer and assess the survival outcome combined with eastern cooperative oncology group performance status (ECOG PS). METHODS: We included 1767 older adults with cancer (66.2% males, 70.97 ± 5.49 years old) from a prospective cohort study. Fifteen systemic inflammatory biomarkers were compared to identify the optimal biomarker using prognostic area under the curve (AUC) and concordance index (C-index) analysis. The prognostic value of the clinical parameters was elucidated by performing uni- and multivariate analyses. RESULTS: The AUC, C-index, and the subgroup survival analysis of ECOG PS groups showed that the lymphocyte-C reactive protein ratio (LCR) and C-reactive protein/albumin ratio (CAR) were more accurate in reflecting patient prognosis than the other 13 inflammatory markers. Compared with patients in the high LCR group, those in the low LCR group had worse survival (hazard ratio (HR) 1.64, 95% confidence interval (95%CI) 1.42-1.91, p < 0.001). Compared with patients in the low CAR group, those in the high CAR group had worse survival (HR 1.65, 95% CI 1.43-1.91, p < 0.001). Older adults with cancer with an ECOG PS score of 2 or 3-4 and a high inflammation (low LCR, 13.3 months and 9.2 months, respectively; or high CAR, 9.6 months and 9.6 months, respectively) had shorter median survival time compared to those with an ECOG PS score of 0/1 and a low inflammation (high LCR, 77.4 months; or low CAR, 77.0 months). CONCLUSION: LCR and CAR might be the better predictive immune inflammatory factors for OS, which improved the survival prediction of different ECOG PS groups in older adults with cancer. High ECOG PS (≥2) and high inflammation increased the risk of death in older adults with cancer.

Glycosylated Zein Composite Nanoparticles for Efficient Delivery of Betulinic Acid: Fabrication, Characterization, and In Vitro Release Properties.

Betulinic acid (BA) has anti-inflammatory, antioxidative stress, and antitumor activities, but BA bioavailability is low due to its poor water solubility and short half-life. This study aimed to construct a BA delivery system to improve its utilization in vitro. Glycosylated zein (G-zein) was prepared using the wet heating method, and BA-loaded zein composite nanoparticles were prepared using the antisolvent method. Compared to zein, G-zein had the advantages of higher solubility and lower surface hydrophobicity. The encapsulation efficiency of G-zein@BA reached over 80% when the BA concentration was 1 mg/mL. Compared to zein@BA nanoparticles, G-zein@BA was characterized by smaller droplets, higher encapsulation efficiency, and a more stable morphology. The sustained release and solubility of G-zein@BA nanoparticles were also superior to those of zein@BA. Compared with free BA, the dispersions of zein@BA and G-zein@BA nanoparticles in water increased 2.27- and 2.91-fold, respectively. In addition, zein@BA and G-zein@BA nanoparticles markedly inhibited the proliferation of HepG2 cells. This study provides new insights into the structural properties and antitumor activity of BA composite nanoparticles to aid in the development of zein particles as functional materials to deliver bioactive compounds.