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The aim of this study was to evaluate the prognostic value of peripheral blood inflammation indexes in patients with metastatic Colorectal Cancer (CRC) and to establish a predictive scoring system. A total of 324 CRC patients diagnosed through pathological examination from January 2017 to July 2022 at the Third Affiliated Hospital of Kunming Medical University were included. The prognosis of patients with metastatic CRC was examined, and the correlation between IL-10 expression in pathological tissues and IL-10 expression in serum was analyzed. The results showed that the prognosis of CRC was poorer when metastasis occurred (P < 0.001). Additionally, IL-10 was highly expressed in the metastatic CRC group (P = 0.018), and the expression of IL-10 in pathological tissues of patients with metastatic CRC was positively correlated with the expression of IL-10 in serum (P = 0.037). The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-white blood cell ratio (LWR), aggregate index of systemic inflammation (AISI), monocyte-to-lymphocyte ratio (MLR), systemic inflammatory response index (SIRI), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI), and interleukin-10 (IL-10) were calculated and determined by ROC curve. The critical values were 2.135, 3.735, 353.745, 0.265, 1.025, 52.975, 353.635, and 11.25, respectively. Inflammatory indexes with an AUC of more than 0.6 were selected, and each colorectal cancer patient with any of these risk factors was assigned a score of one. The 324 patients were then divided into two groups: 0-4 for the low-risk group and 4-8 for the high-risk group. The occurrence of distant metastases in the two groups was statistically analyzed. The results showed that the OS and PFS of the low-risk group were significantly superior to those of the high-risk group (P < 0.05). These findings indicate that NLR, LWR, AISI, MLR, SIRI, PNI, ALI, and IL-10 are risk factors for distant metastasis in CRC patients. Therefore, the prediction scores of these indexes can be used to effectively evaluate the prognosis of patients with metastatic CRC.

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Brown adipose tissue (BAT) plays a critical role in regulating cardiovascular homeostasis through the secretion of adipokines, such as fibroblast growth factor 21 (FGF21). Dexmedetomidine (DEX) is a selective α2-adrenergic receptor agonist with a protection against myocardial ischemia/reperfusion injury (MI/RI). It remains largely unknown whether or not BAT-derived FGF21 is involved in DEX-induced cardioprotection in the context of MI/RI. Herein, we demonstrated that DEX alleviated MI/RI and improved heart function through promoting the release of FGF21 from interscapular BAT (iBAT). Surgical iBAT depletion or supplementation with a FGF21 neutralizing antibody attenuated the beneficial effects of DEX. AMPK/PGC1α signaling-induced fibroblast growth factor 21 (FGF21) release in brown adipocytes is required for DEX-mediated cardioprotection since blockade of the AMPK/PGC1α axis weakened the salutary effects of DEX. Co-culture experiments showed that DEX-induced FGF21 from brown adipocytes increased the resistance of cardiomyocytes to hypoxia/reoxygenation (H/R) injury via modulating the Keap1/Nrf2 pathway. Our results provided robust evidence that the BAT-cardiomyocyte interaction is required for DEX cardioprotection, and revealed an endocrine role of BAT in DEX-mediating protection of hearts against MIRI.

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Background: Chronic kidney disease (CKD) patients undergoing peritoneal dialysis face numerous challenges that can impact their health behaviors, treatment adherence, and overall quality of life. A comprehensive health education program tailored for CKD patients on peritoneal dialysis is imperative to enhance the effectiveness of treatment and address these issues. Objective: The primary objective was to evaluate the impact of a full course health education program on health behaviors, treatment adherence, quality of life, and the occurrence of adverse events in CKD patients receiving peritoneal dialysis. Methods: A total of 98 CKD patients on peritoneal dialysis at our hospital between October 2019 and October 2022 were selected. The patients were randomly assigned to receive either routine care (n=52) or participate in a full-course health education program (n=46). The comparative assessments included health behavior scores, treatment adherence, Kidney Disease Targeted Area (KDTA) scores, monitoring adverse events, and tracking readmissions. Results: Patients in the observation group who underwent the full course health education program exhibited significant improvements in health behavior scores and treatment adherence (P < .05). Notably, the observation group demonstrated higher levels of medication compliance, timely reviews, and catheter maintenance. Moreover, full-course health education contributed to an enhanced quality of life, reflected in higher KATA scores, and led to a reduction in adverse events and readmission rates compared to routine care (P < .05). Conclusions: This study concludes that a full-course health education program is effective in improving health behaviors, treatment adherence, and quality of life while reducing adverse events among CKD patients undergoing peritoneal dialysis.

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BACKGROUND: Diabetic kidney disease (DKD) is a prevalent complication of diabetes that often requires hemodialysis for treatment. In the field of nursing, there is a growing recognition of the importance of humanistic care, which focuses on the holistic needs of patients, including their emotional, psychological, and social well-being. However, the application of humanistic nursing in the context of hemodialysis for DKD patients remains relatively unexplored. AIM: To explore the experience of humanistic nursing in hemodialysis nursing for DKD patients. METHODS: Ninety-six DKD patients treated with hemodialysis from March 2020 to June 2022 were included in the study and divided into the control cluster (48 cases) and the study cluster (48 cases) according to different nursing methods; the control cluster was given routine nursing and the study cluster was given humanized nursing. The variances of negative emotion mark, blood glucose, renal function, the incidence of complications, life mark and nursing satisfaction before and after nur-sing were contrasted between the two clusters. RESULTS: No significant difference in negative emotion markers between the two clusters were observed before nursing (P > 0.05), and the negative emotion markers of the two clusters decreased after nursing. The Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale markers were lower in the study cluster than the control cluster. The healing rate of patients in the study cluster was significantly higher than the control cluster (97.92% vs 85.42%, P < 0.05). Blood glucose parameters were not significantly different between the groups prior to nursing (P > 0.05). However, after nursing, blood urea nitrogen and serum creatinine (SCr) levels in the study cluster were lower than those in the control cluster (P < 0.05). The incidence rate of complications was significantly lower in the study group compared to the control cluster (6.25% vs 20.83%, P < 0.05). There was no significant difference in the life markers between the two clusters before nursing. While the life markers increased after nursing for both groups, the 36-item health scale markers in the study cluster were higher than those within the control cluster (P < 0.05). Finally, the nursing satisfaction rate was 93.75% in the study cluster, compared to 75% in the control cluster (P < 0.05). CONCLUSION: In hemodialysis for DKD patients, the implementation of humanistic nursing achieved ideal results, effectively reducing patients' psychological negative emotion markers so that they can actively cooperate with the diagnosis and nursing, facilitate the control of blood glucose and the maintenance of residual renal function, reduce the occurrence of complications, and finally enhance the life quality and nursing satisfaction of patients. It is worthy of being widely popularized and applied.

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Objective: To investigate the impact of affective care on poor mood, quality of life, and self-efficacy in patients with chronic primary kidney disease. Methods: Between January 2020 and January 2021, 112 patients treated in our hospital were divided into a control group (n=55, receiving conventional care) and a research group (n=57, using emotional nursing in addition to conventional care), and the anxiety self-assessment scale (SAS) scores, depression self-assessment scale (SDS) scores, kidney disease quality of life (KDQOL-SF) scores, and the quality of life (KDQOL-SF) scores developed by the Center for Chronic Disease Education, Stanford University, USA were compared before and aftercare. The results of the study group were compared with those of the KDQOL-SF, the Self-Efficacy Scale developed by the Center for Chronic Disease Education and Research, Stanford University, USA, and the adherence to care. Results: After the intervention, the research group had lower SAS and SDS scores than the control group (P < .05). After the intervention, all KDQOL-SF scores and all self-efficacy scores were higher in the research group than in the control group (P < .05). The research group had a higher nursing care adherence rate of 92.98% than the control group of 78.18% (P < .05). Conclusion: Emotional nursing can help improve the poor mood of patients with chronic primary kidney disease, improve their quality of life, and strengthen their self-efficacy, and the overall nursing compliance of patients is higher, which is of high clinical application.

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This study investigated the effect of nano-selenium (nano-Se) in protecting laying hens from mercury (Hg)-induced prehierarchical follicular atresia. Furthermore, the endoplasmic reticulum stress (ERS) was explored to reveal the molecular mechanism. In vivo, 720 Hyline-Brown laying hens were treated with Hg and nano-Se alone or in combination. In vitro, the prehierarchical follicles were treated with Hg, nano-Se and 4-phenyl butyric acid (4-PBA) alone or in combination (Control, 25 µM Hg group, 10 µM nano-Se group, 20 µM nano-Se group, 25 µM Hg + 10 µM nano-Se group, 25 µM Hg + 20 µM nano-Se group, 25 µM Hg + 4-PBA group, and 25 µM Hg + 20 µM nano-Se + 4-PBA group). The GCs were treated with Hg and nano-Se alone or in combination (Control, 15 µM Hg group, 6 µM nano-Se group, 12 µM nano-Se group, 15 µM Hg + 6 µM nano-Se group, 15 µM Hg + 12 µM nano-Se group). The results revealed that dietary Hg significantly reduced laying performance (P < 0.05) and egg quality (P < 0.05), whereas nano-Se addition prevented these reductions (P < 0.05). Hg exposure significantly induced the accumulation of Hg in PHFs (P < 0.05), prehierarchical follicular atresia (P < 0.05) and apoptosis in PHFs, whereas nano-Se addition significantly prevented these effects (P < 0.05). The levels of sex hormones (P < 0.05) were significantly decreased after Hg exposure in vivo and in vitro, while nano-Se addition prevented the reductions. Furthermore, the RNA-Seq results showed that the key factors of the ERS presented differential expression, including C/EBP homologous protein, protein kinase RNA-like endoplasmic reticulum kinase (PERK) and activating transcription factor 6 (ATF6) in GCs. Hg exposure significantly increased the key gene expression of endoplasmic reticulum stress in GCs, whereas nano-Se addition prevented the induction of expression of these genes. In addition, the protein levels of PERK, inositol requiring protein 1α (IRE1α) and ATF6 were significantly increased, whereas nano-Se addition prevented the enhancements of protein expression in GCs. In conclusion, this study shows that Hg exposure can reduce induce prehierarchical follicular atresia, whereas nano-Se can prevent these effects. Our results also elucidate a key role of ERS in these protective effects of nano-Se in laying hens.

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This study investigated that the effect of nano-selenium (nano-Se) addition preventing prehierarchical follicular atresia induced by mercury (Hg) exposure in laying hens. Furthermore, endoplasmic reticulum (ER) stress pathway was explored to reveal the protective mechanism of nano-Se in vitro. The results revealed that Hg could significantly reduce laying performance (P < 0.05) and egg quality (P < 0.05), whereas nano-Se addition partially reversed the reductions. Besides, Hg significantly induced the deposition of Hg in prehierarchical follicles (P < 0.05) and prehierarchical follicular atresia (P < 0.05), whereas nano-Se addition could alleviate these toxicities in vitro. In addition, Hg exposure could significantly reduce cell viability (P < 0.05) and induce pyknotic nucleus in prehierarchical granulosa cells, while nano-Se addition reversed these effects. The levels of follicle-stimulating hormone (P < 0.05), luteinizing hormone (P < 0.05), progesterone (P < 0.05), and estradiol (P < 0.05) were significantly decreased after Hg exposure in vitro. However, nano-Se addition reversed the decreases of sex hormone levels. Furthermore, Hg exposure significantly increased the gene expressions of CHOP (P < 0.05), PERK (P < 0.05), ATF4 (P < 0.05), ATF6 (P < 0.05), ASK1 (P < 0.05), IRE1α (P < 0.05), TRAF2 (P < 0.05), caspase-9 (P < 0.05), caspase-3 (P < 0.05), and Bax/Bcl-2 (P < 0.05), whereas nano-Se addition reversed these increases of gene expressions in vitro. In summary, this study provides that Hg can induce prehierarchical follicular atresia, whereas nano-Se addition can ameliorate it, and elucidates an important role of ER stress in nano-Se alleviating prehierarchical follicular atresia induced by Hg in laying hens.

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BACKGROUND: To investigate the status quo of participation in exercise among gastric cancer patients after radical gastrectomy and analyze the influencing factors. METHODS: Convenient sampling was used to conduct a questionnaire survey of 163 patients after radical gastric cancer surgery from January to December 2020. The survey content included general information, exercise participation, exercise knowledge, attitude, and social support. Descriptive statistics, single factor analysis, and multiple linear regression analysis were performed using Statistical Product and Service Solutions 24.0 (SPSS24.0, IBM, USA). RESULTS: After radical gastrectomy, the form of exercise that patients participated in was relatively simple. The average amount of exercise involved was 8.10 Mets-h/week, which was at the level of almost no exercise. Univariate analysis showed that differences in age, gender, education level, work status, main caregivers and sports knowledge, attitudes, and social support levels all led to different levels of exercise participation. Multiple linear regression analysis showed that the factors affecting the patient's level of participation in exercise included age, degree of self-care in life, attitude towards exercise after surgery, and level of social support. CONCLUSIONS: The status quo of exercise participation among gastric cancer patients after radical gastrectomy is not ideal. In this study, we found that age, level of self-care in life, sports attitude, and level of social support were the main factors affecting the exercise participation of patients. Therefore, improving patients' self-care ability, exercise attitude, and increasing social support may play an important role in improving the status quo of patients' exercise participation after radical gastric cancer surgery.

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BACKGROUND: Aerobic exercise is currently considered to be an effective method of rehabilitation in breast cancer patients. Studies have shown that aerobic exercise after breast cancer surgery can improve upper limb function, cardiopulmonary function, and quality of life. Breast cancer rehabilitation guidelines encourage patients to actively participate in aerobic exercise to promote rehabilitation, the current study is to evaluate the effectiveness of aerobic exercise on upper limb muscle strength and range of motion (ROM) following breast cancer treatment. METHODS: Electronic databases (Cochrane Library, PubMed, Web of Science, EBSCO and Embase) were searched for randomized controlled trials (RCTs) published before September 1, 2019, using the search terms "aerobic exercise", "exercise", "breast cancer", "muscle strength", "strength", "flexibility" and "function". Grip strength and shoulder joint ROM were used to evaluate upper limb strength and upper limb flexibility respectively. All statistical tests were performed using RevMan5.3 software. RESULTS: Nine RCTs (421 patients) were included for analysis, with JBI scores ranging from 19 to 23, and bias grade B for all studies among which, there were six studies reported change in grip strength, and five studies reported change in shoulder joint ROM. Meta-analysis showed a statistically significant difference in shoulder flexion ROM (MD =4.97, 95% CI: 0.47-9.46, P=0.03), shoulder abduction ROM (MD =8.95, 95% CI: 0.99-16.91, P=0.03), shoulder internal rotation ROM (MD =3.45, 95% CI: 1.80-5.09, P<0.0001), shoulder external rotation ROM (MD =7.69, 95% CI: 0.06-15.32, P=0.05) between the intervention and control groups following completion of the aerobic exercise intervention, while there were no significant improvement with respect to grip strength and shoulder extension ROM (P>0.05). CONCLUSIONS: Aerobic exercise could improve shoulder joint ROM in breast cancer survivors, but shows no obvious effect on the improvement of upper limb strength.

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Metabolic reprograming is a hallmark of cancer, and the polyamine metabolic network is dysregulated in many cancers. Ornithine decarboxylase (ODC) is a rate-limiting enzyme for polyamine synthesis in the polyamine metabolic network. In many cancer cells, ODC is over-expressed, so this enzyme has been an attracting anti-cancer drug target. In the catalysis axis (pathway), ODC converts ornithine to putrescine. Meanwhile, ODC's activity is regulated by protein-protein interactions (PPIs), including the ODC-OAZ1-AZIN1 PPI axis and its monomer-dimer equilibrium. Previous studies showed that when ODC's activity is inhibited, the PPIs might counteract the inhibition efficiency. Therefore, we proposed that multipurpose inhibitors that can simultaneously inhibit ODC's activity and perturb the PPIs would be very valuable as drug candidates and molecular tools. To discover multipurpose ODC inhibitors, we established a computational pipeline by combining positive screening and negative screening. We used this pipeline for the forward screening of multipurpose ligands that might inhibit ODC's activity, block ODC-OAZ1 interaction and enhance ODC non-functional dimerization. With a combination of different experimental assays, we identified three multipurpose ODC inhibitors. At last, we showed that one of these inhibitors is a promising drug candidate. This work demonstrated that our computational pipeline is useful for discovering multipurpose ODC inhibitors, and multipurpose inhibitors would be very valuable. Similar with ODC, there are a lot of proteins in human proteome that act as both enzymes and PPI components. Therefore, this work is not only presenting new molecular tools for polyamine study, but also providing potential insights and protocols for discovering multipurpose inhibitors to target more important protein targets.

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Covalent ligands modulating protein activities/signals have attracted unprecedented attention in recent years, but the insufficient understanding of their advantages in the early days of drug discovery has hindered their rational discovery and development. This also left us inadequate knowledge on the rational design of covalent ligands, e.g., how to balance the contribution from the covalent group and the noncovalent group, respectively. In this work, we dissected the noncovalent docking from covalent docking by creating SCARs (steric-clashes alleviating receptors). We showed that the SCAR method outperformed those specifically developed but more complicated covalent docking protocols. We furthermore provided a "proof-of-principle" example by implementing this method in the first high-throughput screening and discovery of novel covalent inhibitors of S-adenosylmethionine decarboxylase. This work demonstrated that noncovalent groups play a predeterminate role in the design of covalent ligands, and would be of great value in accelerating the discovery and development of covalent ligands.

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