Feasibility of the enhanced neuromuscular blockade recovery protocol with selective use of sugammadex in thyroid surgery with intraoperative neuromonitoring.

BACKGROUND: To investigate feasibility of utilizing enhanced neuromuscular blocking agents with selective recovery protocol during thyroid surgery with intraoperative neuromonitoring (IONM). METHODS: Two-hundred and ninety patients were randomized into two groups: group A 0.3 mg/kg rocuronium and group B 0.6 mg/kg. Sugammadex 2 mg/kg was injected if needed followed initial vagal stimulation (V0). Electromyography signals from vagus and recurrent laryngeal nerves before and after resection were recorded as V1, V2, R1, and R2. RESULTS: In group B, 30 patients (20.7%) had V0 signals <100 µV, compared to 9 (6.2%) in group A. After sugammadex administration, 144 patients (99.3%) in both groups achieved positive V1 signals. Group B demonstrated a shorter surgical time from rocuronium injection to V2 stimulation compared to group A, accompanied by a significantly lower incidence of intraoperative body movement (0 vs. 16 patients). CONCLUSIONS: 0.6 mg/kg rocuronium with selective use 2 mg/kg sugammadex for IONM in thyroid surgery can meet both anesthesia and surgery demands.

Finding the minimum number of retrieved lymph nodes and negative lymph nodes in gastric cancer surgery: a real-world study.

BACKGROUND: Lymph node retrieval deficiency can lead to understagement and postoperative cancer recurrence, it is crucial to establish the standard number of retrieved lymph nodes (rLNs) and negative lymph nodes (nLNs) for patients undergoing gastrectomy. METHODS: Patients who has gastric adenocarcinoma and underwent either radical subtotal gastrectomy (RSG) or radical total gastrectomy (RTG) between 2000 and 2022 were retrospectively included. We utilized restricted cubic spline (RCS) analysis to determine the ideal threshold for rLNs and nLNs. Survival analysis was conducted using Kaplan-Meier (KM) curves, log-rank tests and forest plots. Propensity score matching (PSM) was utilized to balance parameters between two groups. The median follow-up time for this study was 3,095 days. RESULTS: Our study found that there are significant tumor characteristic differences between RSG and RTG. For patients with N0-N3a stage undergoing RSG, retrieving≥24 lymph nodes intraoperatively were associated with better prognosis both before and after PSM (OS: P<0.001, P=0.019); whereas for N3b stage, at least 32 rLNs were required (OS: P=0.006, P=0.023). Similarly, for patients with N0-N3a stage undergoing RTG, retrieving≥27 lymph nodes intraoperatively were associated with better prognosis both before and after PSM (OS: P<0.001, P=0.047); whereas for N3b stage, at least 34 rLNs were required (OS: P<0.001, P=0.003). Additionally, for patients undergoing RSG, having ≥21 nLNs (OS: P<0.001, P=0.013), and for those undergoing RTG, having ≥22 nLNs (OS: P<0.001, P<0.001), were also associated with better prognosis both before and after PSM. CONCLUSIONS: For patients receiving RSG, rLNs should reach 24 when lymph nodes are limited, and 32 when lymph node metastasis is more extensive, with a minimum number of nLNs ideally reaching 21. Similarly, for patients receiving RTG, rLNs should reach 27 when lymph nodes are limited, 34 when lymph node metastasis is more extensive, and a minimum number of nLNs ideally reaching 22.

Preventing lower limb lymphedema after pelvic lymphadenectomy with progressive resistance exercise training: A randomized controlled trial.

Objective: This study aimed to assess the efficacy of a self-designed progressive resistance exercise training program for preventing the development of lower limb lymphedema. Methods: An open-label randomized controlled trial was conducted in patients who underwent radical surgery for cervical cancer treatment in our department between October 7, 2019, and October 7, 2021. The participants were randomly assigned to one of three groups: progressive resistance exercise training, graduated compression stocking, and control group. Results: A total of 267 patients were enrolled (89 in each group). The incidence of lower limb lymphedema was 9.0% (n = 8) in the progressive resistance exercise training group, 28.1% (n = 25) in the graduated compression stocking group, and 42.7% (n = 38) in the control group. Over the 2-year follow-up period, the risk of lower limb lymphedema was significantly lower in the progressive resistance exercise training group than in the control group, with a hazard ratio (HR) (95% confidence interval [CI]) of 0.156 (0.073-0.335). The study was underpowered to demonstrate a statistically significant reduction in risk in the graduated compression stocking group, with an HR (95% CI) of 0.624 (0.376-1.033). Conclusions: Progressive resistance exercise training is an effective strategy for preventing lower limb lymphedema after pelvic lymphadenectomy for cervical cancer. It imposes no additional economic burden and can be performed conveniently without the need for dedicated exercise facilities. This makes it particularly accessible to patients in developing countries, allowing them to exercise at their convenience. Trial registration: ChiCTR1800014905.

Induction Toripalimab and Chemotherapy for Organ Preservation in Locally Advanced Laryngeal and Hypopharyngeal Cancer: A Single-Arm Phase II Clinical Trial.

PURPOSE: The aim of this study was to assess the efficacy, toxicities, and potential role of larynx preservation of induction chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitor in locally advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: This is a single-arm phase II study. Patients with histopathologically confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma and Eastern Cooperative Oncology Group Performance Status 0-1 were eligible. Three cycles of induction chemotherapy (paclitaxel 175 mg/m2 d1, cisplatin 25 mg/m2 d1-3) combined with PD-1 inhibitor (toripalimab 240 mg d0) were administered. Response assessment was performed after induction chemoimmunotherapy using RECIST 1.1 criteria. Patients with a complete/partial response of the primary tumor received concurrent chemoradiation, followed by maintenance therapy of toripalimab. Otherwise, patients were referred to surgery, followed by adjuvant (chemo) radiation and maintenance therapy of toripalimab. The primary endpoint is a larynx preservation rate at 3 months postradiation. RESULTS: Twenty-seven patients were enrolled. Most cases exhibited stage IV disease (81.5%), with T4 representing 37.0%. Five patients underwent pretreatment tracheostomy because of impaired larynx function. Overall response rate of induction chemoimmunotherapy was 85.2%. At 3 months postradiation, the larynx preservation rate was 88.9%. With a median follow-up of 18.7 months, the 1-year overall survival rate, progression-free survival rate, and larynx preservation rate were 84.7%, 77.6%, and 88.7%, respectively. When excluding those with pretreatment tracheostomy, the 1-year larynx preservation rate was 95.5%. Exploratory analysis revealed that relapse correlated with enrichment of RNA signature of hypoxia and M2 macrophage-associated genes. CONCLUSIONS: Induction toripalimab combined with chemotherapy provided encouraging activity, promising larynx preservation rate and acceptable toxicity in this cohort of extensively locally advanced laryngeal and hypopharyngeal cancer.

Diagnostic value of plasma circular RNA based on droplet digital polymerase chain reaction in lung adenocarcinoma.

BACKGROUND: Plasma circular (circ)RNAs detected by droplet digital polymerase chain reaction (ddPCR) may be ideal markers for liquid biopsy. However, ddPCR detection of circRNAs in plasma for diagnosis of lung adenocarcinoma has been rarely reported. METHODS: An RNA sequencing analysis was performed in plasma from patients with early lung adenocarcinoma and healthy individuals. Droplet digital PCR was used to verify the differentially expressed genes. RESULTS: The copy numbers of circle RNALZIC (circLZIC)and circle RNACEP350 (circCEP350) in the plasma of lung adenocarcinoma patients were significantly higher than in plasma of healthy people, and the copy numbers in postoperative plasma of the same patients were significantly lower than those in preoperative plasma. CircLZIC and circCEP350 alone and in combination had diagnostic value in lung adenocarcinoma and early lung adenocarcinoma. CircLZIC and circCEP350 had more binding sites with multiple microRNAs. Their target genes were enriched in several signaling pathways. CONCLUSION: The copy numbers of circLZIC and circCEP350 were higher in plasma of lung adenocarcinoma patients than in plasma of healthy controls, significantly correlated with tumor size and TNM stage, and closely related to the occurrence and development of tumors. These circRNAs may serve as molecular markers for the diagnosis of lung adenocarcinoma.

Effects and potential mechanism of dietary vitamin C supplementation on hepatic lipid metabolism in growing laying hens under chronic heat stress.

The adverse effects of chronic heat stress (CHS)-induced fatty liver syndrome on laying hens during the egg-producing stages have been wildly documented. However, until nowadays, the CHS responses of growing laying hens as well as its alleviating effects of vitamin C are rarely reported. In this study, 12-wk-old laying hens were subjected to CHS at 36 °C for 10 h/d for 3 wk with or without dietary supplementation of 300 mg/kg vitamin C. Results showed that CHS significantly impaired the growth performances and the liver functions of birds, as characterized by reduced feed intake and body weight, increased hepatic lipid accumulation and serum concentrations of TG, ALT, and AST, as well as the abnormal expression patterns of the lipid metabolism-related genes. Vitamin C supplementation successfully mitigated the lipid accumulation, while showing no alleviating effect on the serum contents of ALT or AST, which are two key indicators of liver functions. Metabolomic analysis based on UPLC-Q-TOF/MS identified 173 differential metabolites from the HS and HSV group samples, and they are mainly enriched in the pathways related to the cellular components, vitamin and amino acid metabolism and energy substance metabolism. The results indicate that CHS-induced hepatic lipid deposition in growing laying hens is effectively alleviated by dietary supplementation of vitamin C, which is probably resulted from the alterations of hepatocellular metabolic patterns.

Chronic heat stress (CHS)-induced fatty liver syndrome (FLS) is one of the major problems faced in poultry industry. However, the heat stress response as well as the alleviating strategies for growing laying hens is rarely concerned until nowadays. In this study, 12-wk-old laying hens were subjected to the CHS condition with or without dietary supplementation of 300 mg/kg vitamin C, we found that CHS can also remarkably impair the growth performance and liver functions and induce the hepatic lipid metabolism disorders in the growing laying hens. Vitamin C supplementation successfully mitigated the hepatic lipid accumulation, while showed no alleviating effect on the liver functions. Metabolomic analysis further identified 173 differential metabolites between CHS and HSV groups, which are mainly enriched in the pathways including the cellular components, vitamin and amino acid metabolism and the energy substance metabolism. The results suggest that vitamin C supplementation can effectively alleviate the hepatic lipid deposition in growing laying hens under CHS probably through altering their energy metabolism patterns.

Red cell distribution width-a potential prognostic indicator for colorectal cancer patients after radical resection in China.

Background: Red cell distribution width (RDW) can signal poor prognosis in inflammatory medical conditions. The purpose of the study was to investigate the relationship between preoperative RDW and colorectal cancer (CRC) in a large cohort of patients. Methods: A total of 6,224 CRC patients who underwent radical resection at the Fudan University Shanghai Cancer Center were evaluated retrospectively. The prognostic significance of RDW for overall survival (OS) and disease-free survival (DFS) was analyzed using Cox proportional hazards models and Kaplan-Meier method. Propensity score matching (PSM) was used based on survival confounding factors. Results: The mean age of the study participants was 59.5±12.0 years and the study cohort was 44% female. The overall median and mean RDW values were 13.3% and 14.0%, respectively. Patients were stratified into three groups based on their RDW value (≤13.3%, 13.4-14.0%, and >14.0%). OS and DFS were shown to significantly deteriorate with increasing RDW category. In the PSM population, OS and DFS were significantly lower in the high RDW group compared with matched controls. However, the differences vanished in the comparisons between the middle RDW group and the control group. Conclusions: Our findings demonstrate that preoperative RDW may represent a simple and powerful prognostic factor for CRC patients after radical resection. Integrating RDW into clinical practice may better inform the prognosis and optimize therapeutic approaches for patients with CRC.

Predictors of cancer screening behavior of the working population in China based on the information-motivation-behavioral skills model.

Background: The cancer screening rate in the working population is very low in China. Information-motivation-behavioral skills (IMB) model has been applied to elucidate screening behavior for various chronic diseases but has not been investigated in analyzing cancer screening behavior. This study aimed to examine factors influencing cancer screening behavior and their linkages based on the IMB model. Methods: A cross-sectional study was conducted in Shanghai, China from August to October 2021. Data were obtained through an anonymous questionnaire. Predictive relationships between variables in the IMB model and cancer screening behavior were evaluated. Structural equation modeling (SEM) was constructed to demonstrate the utility of the IMB model. Results: Among the 556 participants included in the analysis, 34.4% of participants had ever done a cancer screening. The construct validation analysis supported that the measure items included were acceptable. SEM found that knowledge of cancer warning signs and symptoms (ß = 0.563, p < 0.001) and cancer screening behavioral skills (ß = 0.264, p = 0.003) were related to participation in cancer screening, whereas cancer screening motivation was not directly influenced the participation in cancer screening (ß = - 0.075, p = 0.372). Conclusion: The cancer screening rate was found to be lower than expected in the working population. The IMB model could be used to make decisions in implementing behavioral interventions to participate in cancer screening among the Chinese working population. Enhancing the knowledge of cancer warning signs and symptoms and strengthening behavioral skills should be focused on to improve participation in cancer screening.

Favorable prognosis of breast cancer brain metastases patients with limited intracranial and extracranial metastatic lesions.

BACKGROUND: Breast cancer brain metastases (BCBM) are highly heterogenous with widely differing survival. The prognosis of the oligometastatic breast cancer (BC) patients with brain metastases (BM) has not been well studied. We aimed to investigate the prognosis of BCBM patients with limited intracranial and extracranial metastatic lesions. METHODS: Four hundred and forty-five BCBM patients treated between 1st January 2008 and 31st December 2018 at our institute were included. Clinical characteristics and treatment information were obtained from patient's medical records. The updated breast Graded Prognostic Assessment (Breast GPA) was calculated. RESULTS: The median OS after diagnosis of BM were 15.9 months. Median OS for patients with GPA 0-1.0, 1.5-2, 2.5-3 and 3.5-4 were 6.9, 14.2, 21.8, 42.6 months respectively. The total number of intracranial and extracranial metastatic lesions, in addition to the Breast GPA, salvage local therapy and systemic therapy (anti-HER2 therapy, chemotherapy and endocrine therapy) were demonstrated to be associated with prognosis. One hundred and thirteen patients (25.4%) had 1-5 total metastatic lesions at BM diagnosis. Patients with 1-5 total metastatic lesions had a significantly longer median OS of 24.3 months compared to those with greater than 5 total metastatic lesions with a median OS of 12.2 months (P < 0.001; multivariate HR 0.55, 95% CI, 0.43-0.72). Among the patients with 1-5 metastatic lesions, median OS for GPA 0-1.0 was 9.8 months, compared to 22.8, 28.8 and 71.0 for GPA 1.5-2.0, 2.5-3.0 and 3.5-4.0 respectively, which is much longer than the corresponding patients with greater than 5 total metastatic lesions, with medium OS of 6.8, 11.6, 18.6 and 42.6 months respectively for GPA 0-1.0, 1.5-2.0, 2.5-3.0 and 3.5-4.0. CONCLUSIONS: The patients with 1-5 total metastatic lesions demonstrated better OS. The prognostic value of the Breast GPA and the survival benefit of salvage local therapy and continuation of systemic therapy after BM were confirmed.

Alleviation effect of conjugated linoleic acid on estradiol benzoate induced fatty liver hemorrhage syndrome in Hy-line male chickens.

The purpose of this study was to explore whether conjugated linoleic acid (CLA) could alleviate fatty liver hemorrhagic syndrome (FLHS) induced by estradiol benzoate intramuscular injection in laying hens. One hundred male Hy-Line white chickens were randomly divided into two groups, namely, the control (CON) and estradiol benzoate (E) groups, and both groups were fed the same basal diet. After injections of estradiol benzoate at 2 mg/kg every two days for a total of 7 times, chickens in the E group showed FLHS symptoms, including liver enlargement, hemorrhage, and steatosis. Then half of the chickens in the E group received an additional diet containing 5000 mg/kg CLA for 8 weeks. The results of morphological observations, hematoxylin and eosin staining, and Oil Red O staining showed that CLA alleviated liver enlargement, hemorrhage, and lipid accumulation in FLHS chickens. In addition, we measured liver function and lipid metabolism indicators, including ALT, AST, TG, TCH, HDL-C, and LDL-C, which further suggested that CLA mitigated the disturbance of serum and liver metabolism in FLHS chickens. Mechanistically, CLA inhibited hepatic de novo lipogenesis, cholesterol synthesis, and TG accumulation and increased TG hydrolysis in FLHS chickens by regulating the gene expression of CD36, ACC, FAS, SCD 1, DGAT2, LIPE, ATGL, CPT1A, SREBP-1c, SREBP-2, PPARγ, and PPARα. Furthermore, CLA ameliorated hepatic oxidative stress and inhibited NF-κB signaling pathway-mediated inflammation in FLHS chickens. In conclusion, CLA regulated lipid metabolism, thus further alleviating oxidative stress and inflammation to alleviate FLHS induced by estrogen in chickens.

Fatty liver hemorrhagic syndrome (FLHS) has become one of the most common noninfectious diseases that contribute to laying hen mortality. Conjugated linoleic acid (CLA) is a functional polyunsaturated fatty acid with antioxidant and anti-inflammatory properties The purpose of this study was to investigate the effect of CLA on FLHS induced by estradiol benzoate in laying hens. We successfully replicated the FLHS pathological model by intramuscular injection of estradiol benzoate. The results of morphological and histopathological observations showed that CLA alleviated liver lipid accumulation in FLHS chickens. In addition, we measured liver function and lipid metabolism indicators, which further suggested that CLA mitigated the disturbance of serum and liver metabolism in FLHS chickens. Moreover, CLA inhibited hepatic de novo lipogenesis, cholesterol synthesis, and TG accumulation and increased TG hydrolysis in FLHS chickens by regulating related gene expression. Furthermore, CLA ameliorated hepatic oxidative stress and inhibited inflammation in FLHS chickens. In conclusion, CLA regulated lipid metabolism, thus further alleviating oxidative stress and inflammation to alleviate FLHS induced by estrogen in chickens. Our results provide new evidence and insights for applying CLA as an effective treatment for FLHS.

Effects of N-acetyl-l-cysteine on chronic heat stress-induced oxidative stress and inflammation in the ovaries of growing pullets.

The aims of this study were to investigate the effects of supplemental N-acetyl-l-cysteine (NAC) on chronic heat stress-induced oxidative stress and inflammation in the ovaries of growing pullets. A total of 120, 12-wk-old, Hy-Line Brown hens were randomly separated into 4 groups with 6 replicates of 5 birds in each group for 21 d. The 4 treatments were as follows: the CON group and CN group were supplemented with basal diet or basal diet with 1 g/kg NAC, respectively; and the HS group and HSN group were heat-stressed groups supplemented with basal diet or basal diet with 1 g/kg NAC, respectively. The results indicated that the ovaries suffered pathological damage due to chronic heat stress and that NAC effectively ameliorated these changes. Compared with the HS group, antioxidant enzyme activities (including SOD, GSH-Px, CAT, and T-AOC) were enhanced, while the MDA contents and the expression levels of HSP70 were decreased in the HSN group. In addition, NAC upregulated the expression levels of HO-1, SOD2, and GST by upregulating the activity of Nrf2 at different time points to mitigate oxidative stress caused by heat exposure. Simultaneously, NAC attenuated chronic heat stress-induced NF-κB pathway activation and decreased the expression levels of the proinflammatory cytokines IL-8, IL-18, TNF-α, IKK-α, and IFN-γ. Cumulatively, our results indicated that NAC could ameliorate chronic heat stress-induced ovarian damage by upregulating the antioxidative capacity and reducing the secretion of proinflammatory cytokines.

Antioxidative and anti-inflammatory effects of vitamin C on the liver of laying hens under chronic heat stress.

In this study, we investigated the therapeutic effect and mechanism of action of vitamin C on chronic heat stress (CHS)-induced liver oxidative damage and inflammation in laying hens. The thermoneutral control group (TN group) was kept at a constant temperature of 22 ± 1°C, while the chronic heat stress group (CHS group) and the vitamin C supplemented group (HSV group) were exposed to heat stress (HS) (36 ± 1°C, 8 h/d). The TN and HS groups were fed the basic diet at will, and the HSV group was supplemented with 300 mg/kg of vitamin C on top of the basic diet. The experimental results showed a significant improvement in body weight and feed intake in the HSV group compared to the HS group. A significantly lower pH and higher HCO 3 - and PCO2 levels were observed in the HSV group compared to the CHS group. As laying hens were supplemented with vitamin C, serum malondialdehyde (MDA) level was declined, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were increased, and total antioxidant capacity (T-AOC) was increased. Further, CHS induced an increase in the expression of inflammation-related genes and a decrease in the expression of antioxidant-related genes. In contrast, the addition of vitamin C reversed the effects of CHS, resulting in an increase in the expression of antioxidant-related genes and a decrease in the expression of inflammation-related genes. In conclusion, vitamin C can effectively alleviate CHS-induced acid-base imbalance in body fluids of laying hens and the oxidative damage and inflammatory response caused to the liver. Therefore, vitamin C can be used clinically as an effective drug to alleviate chronic heat stress in laying hens. This experiment provides clinical evidence and theoretical basis for the use of vitamin C as an effective drug to alleviate chronic heat stress in laying hens.

Application Value of Management Model Based on "Zero Tolerance" Concept in Pressure Ulcer Management.

Background: Pressure injuries are the most prevalent health problem worldwide. Improving the quality of hospital pressure injury management is an important indicator to improve the quality of hospital management. Objective: To explore the application value of the management model centered on the concept of "zero tolerance" in the management of pressure ulcers (PU). Methods: The effects of conventional management mode and management mode centered on the concept of "zero tolerance" on PU patients and nursing staff were retrospectively analyzed. The patients were evaluated by the general comfort questionnaire (GCQ), Generic Quality of Life Inventory 74 (GQOL-74), and pressure ulcer healing scale (PUSH). At the same time, the satisfaction of PU patients and nursing staff with different management modes was investigated. Results: When comparing the conditions of patients under different management modes, it was found that the "zero tolerance" management mode can improve the comfort and quality of life of patients during hospitalization. Compared with the conventional management mode, the "zero tolerance" management mode can significantly improve the degree of pressure ulcer healing in patients. In addition, the "zero tolerance" management model can not only improve the satisfaction of patients with management but also improve the satisfaction of nursing staff with management. Conclusion: Standardized management of PU patients with the concept of "zero tolerance" as the core can improve the health status and quality of life of patients, promote wound healing, and improve the satisfaction of patients and nurses with the management plan.

Anemia tolerance versus blood transfusion on long-term outcomes after colorectal cancer surgery: A retrospective propensity-score-matched analysis.

Background: Perioperative anemia and transfusion are intertwined with each other, and both have adverse impacts on the survival of colorectal cancer (CRC) patients. But the treatment of anemia still relies on transfusion in several countries, which leads us to question the effects of anemia tolerance and transfusion on the long-term outcomes of CRC patients. We investigated the combined effect of preoperative anemia and postoperative anemia and of preoperative anemia and blood transfusion, which imposes a greater risk to survival, to compare the effects of anemia tolerance and transfusion on overall survival (OS) and disease-free survival (DFS) in patients undergoing CRC surgery. Methods: A retrospective propensity-score-matched analysis included patients with CRC undergoing elective surgery between January 1, 2008, and December 31, 2014. After propensity-score matching, Kaplan-Meier survival analysis and univariable and multivariable Cox proportional hazards models were used to study the prognostic factors for survivals. In univariate and multivariate Cox regression analysis, two novel models were built. Results: Of the 8,121 patients with CRC, 1,975 (24.3%) and 6,146 (75.7%) patients presented with and without preoperative anemia, respectively. After matching, 1,690 patients remained in each group. In the preoperative anemia and postoperative anemia model, preoperative anemia and postoperative anemia was independent risk factor for OS (HR, 1.202; 95% CI, 1.043-1.385; P=0.011) and DFS (HR, 1.210; 95% CI, 1.050-1.395; P=0.008). In the preoperative anemia and transfusion model, preoperative anemia and transfused was the most dangerous independent prognostic factor for OS (HR, 1.791; 95% CI, 1.339-2.397; P<0.001) and DFS (HR, 1.857; 95% CI, 1.389-2.483; P<0.001). In patients with preoperative anemia, the OS and DFS of patients with transfusion were worse than those of patients without transfusion (P=0.026 in OS; P=0.037 in DFS). Conclusions: Preoperative anemia and blood transfusion imposed a greater risk to OS and DFS in patients undergoing CRC surgery, indicating that the harm associated with blood transfusion was greater than that associated with postoperative anemia. These findings should encourage clinicians to be vigilant for the timely prevention and treatment of anemia, by appropriately promoting toleration of anemia and restricting the use of blood transfusion in patients with CRC.

Prognostic significance of tumor deposits in radically resected gastric cancer: a retrospective study of a cohort of 1915 Chinese individuals.

BACKGROUND: Tumor deposits (TDs) have been identified as an independent prognostic factor in gastric cancer (GC). However, the associated clinicopathological factors and how to simply and reasonably incorporate TD into the TNM staging system remain undetermined. The aim of the current study was therefore to assess the significance of TD among radically resected GC patients. METHODS: We retrospectively reviewed 1915 patients undergoing radical resection between 2007 and 2012. The patients were classified into two groups according to TD status (absent vs. present), and the clinicopathologic characteristics, DFS, and OS were compared. Associations of TD presence with other clinicopathologic factors were evaluated by logistic regression analysis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic factors for DFS and OS in the primary cohort. Propensity score matching (PSM) was performed to reduce the possibility of selection bias according to the presence of TD. External validation of previously proposed modified staging systems incorporating TD was conducted. RESULTS: The detection rate of TD was 10.5% (201/1915). The presence of TD was significantly related to unfavorable clinicopathologic variables, including advanced T and N categories. According to the multivariate Cox regression analysis, the presence of TD was identified as an independent prognostic factor for DFS and OS in the primary cohort (both P < 0.001). In the after-PSM cohort, TD presence also significantly shortened DFS and OS. In the external validation, one system that incorporated TD into the pTNM stage had the best performance. CONCLUSIONS: The presence of TD was significantly associated with poor survival in radically resected GC patients. The incorporation of TD into the TNM staging system can further improve the predictive capability. A multicenter cohort with a large sample size is needed to determine the appropriate method of incorporation.

Inhibition of Hepatic AMPK Pathway Contributes to Free Fatty Acids-Induced Fatty Liver Disease in Laying Hen.

Metabolism-associated fatty liver disease (MAFLD) is one of the most common causes of liver disease; however, the underlying processes remain unknown. This study aimed to investigate the changes of free fatty acids (FFA) on the expression of genes related to the AMP-activated protein kinase (AMPK) signaling pathway in the primary hepatocytes of laying hens. The primary hepatocytes of laying hens were treated with FFA (containing a 2:1 ratio of oleic and palmitic acids) for 24 h. FFA significantly increased lipid droplet accumulation, decreased glycogen synthesis, increased the levels of triglycerides (TG), total cholesterol (TC), reactive oxygen species (ROS), malondialdehyde (MDA), and glucose content in the supernatant (GLU) in the primary hepatocytes of laying hens, and decreased the levels of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD), as well as mitochondrial membrane potential (MMP). The results of the PCR array combined with Western blotting experiments showed that the activity of AMPK was inhibited. Inhibition of AMPK signaling pathway decreases the expression of genes involved in fatty acid oxidation, increases the expression of genes involved in lipid synthesis, decreases the expression of genes involved in glycogen synthesis, increases the expression of genes involved in glycolysis, increases the expression of genes involved in oxidative stress, and increases the expression of genes involved in cell proliferation and apoptosis. Taken together, our results suggest that FFA can affect the homeostasis of the AMPK signaling pathway by altering energy metabolic homeostasis, inducing oxidative stress, and adjusting the onset of cell proliferation and apoptosis.

Increased MPO in Colorectal Cancer Is Associated With High Peripheral Neutrophil Counts and a Poor Prognosis: A TCGA With Propensity Score-Matched Analysis.

Background: Myeloperoxidase (MPO) has been demonstrated to be a local mediator of inflammation in tissue damage in various inflammatory diseases. Given its controversial effect on colorectal cancer (CRC), there has been growing interest in investigating the role of this enzyme in CRC. The mechanism underlying MPO activity and CRC progression requires further clarification. Methods: The expression and function of MPO in CRC were evaluated using TCGA analysis. TCGA, TIMER, and Human Cell Landscape analyses were used to analyze the correlation between MPO expression and neutrophil infiltration in CRC. Spearman's bivariate correlation analysis was used to verify the correlation between MPO levels in CRC and the peripheral neutrophil count. In the clinical analysis, 8,121 patients who underwent elective surgery for CRC were enrolled in this retrospective cohort study from January 2008 to December 2014. Propensity score matching was used to address the differences in baseline characteristics. The Kaplan-Meier method and Cox regression analysis were used to identify independent prognostic factors in patients with CRC. Results: MPO was upregulated in CRC tissues, which is related to malignant progression and worse survival in CRC patients from TCGA analysis. MPO was significantly correlated with the infiltration level of neutrophils in CRC in TCGA, TIMER, and Human Cell Landscape analyses. MPO was positively correlated with the peripheral neutrophil count. Data of the 8,121 patients who underwent CRC surgery were available for analysis. After propensity score matching, 3,358 patients were included in each group. Kaplan-Meier survival curves showed that high preoperative neutrophil levels were associated with decreased overall survival (OS; P < 0.001) and disease-free survival (DFS; P = 0.015). The preoperative neutrophil count was an independent risk factor for OS (hazard ratio [HR], 1.157; 95% confidence interval [CI], 1.055-1.268; P = 0.002) and DFS (HR, 1.118; 95% CI, 1.009-1.238; P = 0.033). Conclusions: Our research indicates that increased MPO levels in CRC are significantly correlated with high preoperative neutrophil counts, and both serve as prognostic indicators for worse survival in CRC patients. Our study suggests that neutrophils may be key players in the mechanism linking MPO levels with poor CRC outcomes.

Hepatic resection prolongs overall survival in the selected patients with nasopharyngeal carcinoma liver metastases.

BACKGROUND: The role of surgery in nasopharyngeal carcinoma liver metastases (NCLM) remains elusive, and the current application is limited. We aim to investigate whether hepatic resection (HR) of NCLM improves survival compared with non-hepatic resection (NHR) treatment. METHODS: One hundred and thirty-three patients with NCLM from 2007 to 2017 were divided into two groups. Propensity score matching (PSM) analysis was used to compare the clinical outcomes. RESULTS: After PSM the median overall survival (OS) and the 1, 3 and 5-year OS rates in HR group were 32.60 months, 86.2%, 37.3% and 37.3%, respectively; while for NHR group these values were 19.57 months, 61.5%, 12.9% and 2.9%, respectively (P = 0.008). Multivariate analysis indicated hepatitis B virus infection (P = 0.029) and hepatic resection (P = 0.018) were independent prognostic factors. CONCLUSION: Our study revealed that hepatectomy yields a survival benefit safely compared with systemic treatments, especially for patients with the size of largest metastasis < 5 cm, unilobar distribution of liver tumor and received unanatomical hepatectomy.

A study protocol of a randomized phase II trial of perioperative chemoimmunotherapy verses perioperative chemoimmunotherapy plus preoperative chemoradiation for locally advanced gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma: the NeoRacing study.

BACKGROUND: Perioperative chemotherapy (ChT) and preoperative chemoradiation (CRT) are both the standard treatments for locally advanced gastric cancer (LAGC). CRT can achieve a higher pathological complete regression (pCR) rate, but whether this higher pCR rate can be transformed into a long-term survival benefit remains inconclusive. Therefore, relevant studies are in progress. On the other hand, immunotherapy has been established for the first-line treatment of advanced gastric cancer (AGC) and has been widely explored in the perioperative setting. The combination of chemotherapy/radiotherapy and immunotherapy may have a synergistic effect, which will lead to a better antitumor effect. The preliminary reports of ongoing studies show promising results, including a further improved pCR rate. However, the preferred treatment combination for LAGC is still not established. To solve this problem, we are carrying out this randomized phase II trial, which aims to evaluate the efficacy and safety of perioperative chemotherapy plus the use of PD-1 antibody with or without preoperative chemoradiation for LAGC. METHODS: Eligible patients with LAGC or gastroesophageal junction (GEJ) adenocarcinoma were randomized to receive perioperative ChT, PD-1 antibody, surgery with (Arm A) or without preoperative CRT (Arm B), and PD-1 antibody maintenance until one year after surgery. The primary endpoint of this study is that the pCR rate of Arm A will be significantly higher than that of Arm B. The secondary endpoints include the pathological partial regression (pPR) rate, R0 resection rate, objective response rate (ORR), event-free survival (EFS), overall survival (OS), safety and surgical complications. Moreover, several explorative endpoints will be evaluated to find and validate the predictive biomarkers of immunotherapy. DISCUSSION: The results of the NeoRacing study will provide important information concerning the application of PD-1 antibody in LAGC patients during the perioperative setting. Meanwhile, the two treatment protocols will be compared in terms of efficacy and safety. TRIAL REGISTRATION: ClinicalTrials.gov , NCT05161572 . Registered 17 December 2021 - Retrospectively registered.

Gut Microbiota and Serum Metabolite Potential Interactions in Growing Layer Hens Exposed to High-Ambient Temperature.

Emerging evidence has revealed the dysbiosis of gut microbiota contributes to development of metabolic diseases in animals. However, the potential interaction between gut microbiota and host metabolism in growing hens under metabolic disorder induced by chronic heat exposure (CHE) remains inconclusive. The aim of our study was to examine the potential association among the cecal microbiota community, physiological indicators, and serum metabolite profiles in CHE hens. One hundred and eighty Hy-Line Brown hens were randomly allocated into three groups: thermoneutral control (TN), heat stress (HS), and pair-fed (PF). The experiment lasted for 5 weeks, with the first 2 weeks serving as the adaptation period. Results showed that the expression level of heat shock protein 70 (HSP70) in both serum and cecal tissues was significantly increased in the HS group. Serum parameters analysis also revealed that CHE caused physiological function damage and metabolic disorders. These results suggest the experiment was successful, inducing chronic heat stress. 16S rRNA sequencing analysis showed that the CHE can clearly induce dysbiosis of the gut microbial community reflected in the increment of the F/B ratio. Besides, serum untargeted metabolomics revealed the relative concentrations of 40 metabolites were significantly altered in the HS group compared with the TN group. Pathway analysis showed that these metabolites were mainly involving the increased proteolysis rather than lipolysis, and this tendency could be a specific metabolic adaptation of the poultry. The pair-feed experiment showed that the above changes induced by CHE were partly independent from the reduction of feed intake. Mantel correlation analysis between gut microorganisms and physiological indicators showed that the phylum Firmicutes and Euryarchaeota have a potential interaction with a serum lipid parameter. Random forest analysis showed that both genus Faecalibacterium and Methanobrevibacter were important predictors of the CHE-induced lipid metabolism disorder. Taken together, our findings may contribute to a better understanding of the metabolic mechanisms underlying the energy metabolism imbalance caused by the CHE and provide novel insights into the host-microbes interactions and its effects on the metabolic adaptation of hens under chronic heat exposure.