Randomized controlled trials on promoting self-care behaviors among informal caregivers of older patients: a systematic review and meta-analysis.

BACKGROUND: Informal caregivers of older patients often neglect their self-care, despite the mental and physical health effects of caregiving. Randomized controlled trials (RCTs) on self-care interventions for informal caregivers are lacking, making it difficult to determine effective strategies. This systematic review explored the definition and categories of self-care RCTs for informal caregivers and a meta-analysis was conducted to determine the effectiveness of these interventions. METHODS: Seven databases (Scopus, Web of Science, MEDLINE, PubMed, ProQuest, CINAHL, and Embase) were searched for articles in English reporting on self-care intervention outcomes for informal caregivers of patients aged 60 years or older. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated using a random-effects model. Subgroup, sensitivity, and publication bias analyses were conducted. RESULTS: Eighteen studies were included in the systematic review, of which fifteen studies were included in the meta-analysis. RCTs lacked a clear definition of self-care, mainly focused on promoting physical and mental health and individual capacity, and neglected disease prevention. The interventions focused on self-management for health and individual agency, with less attention on health literacy, decision-making capacity, self-monitoring for health status, and linkage to the health system. Meta-analysis results showed that RCTs had a small effect on reducing anxiety (SMD = -0.142, 95% CI [-0.302, 0.017], p = .081) but a significant effect on reducing depression (SMD = -0.214, 95% CI [-0.353, -0.076], p = .002). Country and type of caregiver significantly contributed to the effect of reducing caregivers' depression in subgroup analysis. CONCLUSIONS: Studies on caregiver-centered self-care interventions are limited, resulting in a lack of a clear definition and comprehensive intervention. RCTs indicated a small effect on informal caregivers' mental health, and interventions should consider both mental and physical health. More evidence is needed on the effectiveness of self-care interventions for informal caregivers' anxiety and physical health.

Circular RNA PGPEP1 induces colorectal cancer malignancy and immune escape.

OBJECTIVE: Colorectal cancer (CRC) is a prevalent gastrointestinal tumor globally. Circular RNAs (circRNAs) have been identified as regulatory players in the pathogenesis of CRC. However, it is unclear whether hsa_circ_0050102 (circPGPEP1) affects the malignant progression and immune escape in CRC. METHODS: Bioinformatics analysis and circRNA in vivo precipitation experiments were performed to analyze and identify circRNAs that mediate immune escape in CRC. Using luciferase reporter assay, RIP, RNA pull-down assay, and FISH, the interaction between circPGPEP1, miR-515-5p, and nuclear factor of activated T-cell 5 (NFAT5) was identified. The functional role of circPGPEP1/miR-515-5p/NFAT5 axis in CRC anti-tumor immunity was investigated by co-culture assay, CFSE assay, and flow cytometry of CRC cells and T cells. RESULTS: circPGPEP1 was a stable circRNA that was highly expressed in CRC. Functionally, circPGPEP1 silencing not only effectively inhibited CRC cell proliferation, migration, EMT, and immune escape and promoted apoptosis in vitro, but also inhibited CRC tumor growth and immune escape in vivo. In terms of the regulatory mechanism, circIGF2BP3 competitively upregulated NFAT5 expression by sponging miR-515-5p. Furthermore, functional rescue experiments showed that circPGPEP1 acted in CRC by regulating the miR-515-5p/NFAT5 axis. CONCLUSION: Collectively, circPGPEP1 exerts an oncogene role in CRC by regulating the miR-515-5p/NFAT5 axis.

A novel peroxymonosulfate activation process by single-atom iron catalyst from waste biomass for efficient singlet oxygen-mediated degradation of organic pollutants.

Single-atom dispersed catalysts (SACs) have gained considerable attention in organic contaminants remediation due to their superior reactivity and stability. However, the complex and costly synthesis processes limit their practical applications in environmental protection. Herein, a facile and cost-effective single-atom iron catalyst (Fe-SA/NC) anchored on nitrogen-doped porous carbon was first fabricated by using waste biomass as a carbon source. The Fe-SA/NC catalyst exhibited outstanding performance with a high turnover frequency of 1.72 min-1 toward antibiotics degradation via peroxymonosulfate activation. ECOSAR program and algae growth experiments demonstrated that the byproducts produced during the sulfamethoxazole degradation process were not detrimental to the aquatic environment. Radical quenching and electron paramagnetic resonance experiments revealed that Fe-SA/NC remarkably promoted 1O2 production in PMS-assisted reaction, and thus 1O2 contributed as much as 78.77% to sulfamethoxazole degradation. As indicated by experiment and density functional theory (DFT) calculations, FeN2O2 configuration serves as the active site. DFT calculations further presented the most rational generation route of 1O2 as PMS→OH* â†’O* â†’1O2. We also designed Fe-SA/NC embedded spherical pellets for contaminants elimination at the device level. This study offers new insights into the synthesis of SACs from waste biomass and their practical application in environmental remediation.

Clinical feasibility of the therapeutic strategies total neoadjuvant therapy and "watch and wait" in the treatment of rectal cancer patients with recurrence after clinical complete response.

Purpose: In recent years, total neoadjuvant therapy (TNT) has emerged as a new therapeutic strategy against advanced rectal cancer (RC). After administration of TNT, some patients show complete clinical response (cCR) to treatment however, disputes about the effects of TNT and the alternative treatment plans in case of recurrence after cCR still exist. Methods: A total of 100 patients were included in this paper. CR and non-CR was observed when these patients were administered with TNT at the First Affiliated Hospital of Dalian Medical University, China from May 2015 to June 2021. These patients received different chemotherapeutic regimens, with close monitoring and watch and wait (W&W) strategy being applied by a multidisciplinary team (MDT). According to treatment results, patients were divided into a cCR group and a non-cCR group; according to the recurrence during W&W, they were divided into a recurrence group and a no-local-recurrence group. This study analyzed the factors that may affect the prognosis, and summarized the surgery and treatment after recurrence. Results: The TNT strategy was effective, and 85% of patients achieved local remission. However, W&W did not affect the survival time of CR patients, nor did it cause new distant metastasis due to local recurrence during the observation period (P > 0.05). However, for patients with positive CRM, we do not recommend W&W as the first choice of treatment (P < 0.05). Conclusion: (1) Whole-course neoadjuvant therapy was an effective treatment scheme for advanced mid-term rectal cancer. The total local reduction rate of this group of cases was 85.00%, meaning that 25 patients achieved CR. (2) W&W was safe and reliable, and CR patients could receive it as the preferred treatment. (3) CRM was an independent risk factor for local recurrence in CR patients. We do not recommend W&W as the preferred treatment for CR patients with positive CRM.

Peptide SA12 inhibits proliferation of breast cancer cell lines MCF-7 and MDA-MB-231 through G0/G1 phase cell cycle arrest.

BACKGROUND: Targeted therapies have been proven as promising in the treatment of breast cancer and have improved survival and quality of life in advanced breast cancer. We previously identified a novel peptide SA12 which showed significant activity in the inhibition of proliferation and induction of apoptosis in SKBr-3 cells. METHODS: The present study investigated the potential antitumor role of SA12 in breast cancer cell lines MDA-MB-231 and MCF-7 through Cell Counting Kit-8 assay and colony formation assay, and examined the cell cycle distribution using flow cytometry analysis. Furthermore, the expression of cell cycle-related genes cyclin D1, CDK4, and tumor suppressor gene p16 were examined by real-time polymerase chain reaction and Western blot to explore the molecular mechanism. RESULTS: We determined that peptide SA12 suppressed the proliferation of MDA-MB-231 and MCF-7 cell lines through the G0/G1 phase cell cycle arrest. Moreover, the expressions of cell cycle-associated genes cyclin D1 and CDK4 were downregulated and the expression of tumor suppressor gene p16 was upregulated after treatment with SA12. MECP2 was required for the enhanced expression of p16 gene induced by SA12, which further inhibits CDK4/CDK6 activation and arrests the cell cycle progression from G0/G1 to S phase. CONCLUSION: We concluded that SA-12 inhibits the proliferation of MCF-7 and MDA-MB-231 cells through G0/G1 cell cycle arrest. Cell cycle related genes cyclin D1, CDK4, and p16 participate in the process, and MECP2 is essential for the enhanced expression of p16 gene induced by SA-12.

Prediction of chemotherapeutic efficacy using the ratio of neutrophils to lymphocytes in patients with unresectable or recurrent gastric cancer.

In cancer patients, the balance between neutrophil (N) and lymphocyte (L) cell counts fluctuates with the tumor load. The objective of the present study was to determine the implications of the chemotherapy effect by the fluctuations of N/L ratio in patients with unresectable or recurrent gastric cancer. The study participants were identified from a prospective cohort of patients with unresectable or recurrent gastric cancer (n=135). The median N/L ratio was 3.23 (range: 0.76-20.45) prior to chemotherapy (pre-chemo-N/L ratio) and 2.55 (range: 1.17-13.45) following 2-4 weeks from when the chemotherapy was completed (post-chemo-N/L ratio), respectively. The median overall survival was 7.9 months. The results demonstrated that the N/L ratio of the post-chemotherapy was significantly reduced compared with the pre-chemotherapy group (P<0.001). The survival rate for the pre-chemo-N/L ratio ≥4.0 group was significantly reduced compared to the N/L <4.0 group (P=0.01). The difference of the pre-chemo-N/L ratio subtracted from the post-chemo-N/L ratio can inflect the chemotherapy effect, respectively. These results indicate that the N/L ratio may be used to predict the potential chemotherapy efficacy in unresectable or recurrent gastric cancer.

Effect of tumor-associated macrophages on gastric cancer stem cell in omental milky spots and lymph node micrometastasis.

We observed whether the effect of tumor-associated macrophages on gastric cancer stem cell in omental milky spots and lymph nodes micrometastasis and research its possible mechanism. Macrophage THP-1 cells and Human gastric adenocarcinoma SGC-7901 cells were collectively cultivated in vivo. We found macrophage could suppress the proliferation and accelerated cell death of MFC cell. Meanwhile, these effects may be concerned with many signaling pathways, and we detected MCP-1 and COX-2 miRNA expressions, PGE-2 release levels, IL-4 and IL-10 activities, and TGF-ß, IFN-γ, VEGF, MMP-2 and MMP-9 protein expressions in collectively cultivated cell. We found that MCP-1 and COX-2 miRNA expressions, and PGE-2 release levels were suppressed, IL-4 activity was inhibited and IL-10 activity was activated in collectively cultivated cell. Meanwhile, TGF-ß, MMP-2 and MMP-9 protein expressions were inhibited and IFN-γ and VEGF protein expressions were activated in collectively cultivated cell. Taken together, these results suggest that the effect of tumor-associated macrophages on gastric cancer stem cell in omental milky spots and lymph nodes micrometastasis via COX-2/PGE-2/TGF-ß/VEGF signal pathways.

The role of pro-inflammatory cytokines and immune cells in colorectal carcinoma progression.

Cytokines exhibit a pleiotropic effect in the regulation of the immune cell function, tumor growth and antitumor immune responses. A total of 30 patients with colorectal carcinoma were enrolled on this study and their levels of interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, serum granulocyte colony-stimulating factor (sG-CSF) and serum macrophage colony-stimulating factor (sM-CSF) were measured preoperatively using ELISA. Tumor-infiltrating granulocyte (TIG), tumor-associated macrophage (TAM), G-CSF and M-CSF expression in tumor cells were examined using immunostaining. This study revealed abnormal levels of cytokines in patients, including IL-1ß (1/30, 3.3%), IL-6 (16/30 53.3%), IL-81 (15/30, 50%), TNF-α (4/21, 19%), sG-CSF (17/30, 56.7%) and sM-CSF (4/21, 19%). There was a positive linear correlation between IL-6 and sM-CSF (P=0.017, R=0.517). sG-CSF was significantly associated with a deeper tumor invasion (P=0.039) and a more advanced tumor stage (P=0.023). The granulocyte/lymphocyte (G/L) ratio was associated with abnormal levels of sG-CSF. Logistic univariate analysis revealed that TIGs were a risk factor for lymph node metastasis (0.019) and TAMs were a risk factor for depth of invasion (0.029), but this was not confirmed in logistic multivariate analysis. In conclusion, IL-6, IL-8, sM-CSF and sG-CSF may indirectly promote tumor growth, progression and metastasis by changing the leukocyte populations in the blood and the tumor microenvironment.

Activity of antibacterial protein from maggots against Staphylococcus aureus in vitro and in vivo.

Maggots (larvae of Lucilia sericata) have shown therapeutic effects on refractory wounds infected with bacteria, yet the bacterial killing mechanisms are unclear. Herein, we report the isolation and purification of an antibacterial protein from maggots (MAMP). MAMP demonstrated inhibitory activity against both standard strains and clinically isolated antibiotic-resistant strains of Staphylococcus aureus in vitro. The topical use of MAMP effectively decreased the viability of S. aureus and promoted wound healing in an S. aureus mouse skin infection model. MAMP exerted its antibacterial activity via a bactericidal mechanism based on observations using scanning electron and transmission electron microscopy. MAMP interacted with the bacterial cell membrane and disrupted the cell surface structure. In addition, MAMP had weak hemolytic activity at a high concentration. Taken together, MAMP exhibits potential use as a topical agent for treating bacterial infections.

The neutrophil/lymphocyte ratio is an independent prognostic indicator in patients with bone metastasis.

Patients with the most common advanced human cancers such as lung, breast, uterus, and cancers of the digestive system almost always develop bone metastases, with painful and untreatable consequences. This study aimed to determine the prognostic implications of the neutrophil/lymphocyte (N/L) ratio in the peripheral blood of patients with malignant bone metastasis. Study participants were identified from a prospective cohort of cancer patients with bone metastasis. Data for the N/L ratios were obtained from clinical and pathological records and were analyzed together with other known prognostic factors in the multivariate and univariate analyses. The results showed the average N/L ratio of all 497 patients to be 4.25±2.44 (range 0.54-45.50 years). Multivariate analysis revealed that tumor type and a high N/L ratio were significantly associated with poor prognosis. For the high N/L ratio group, the estimated hazard ratio of death was 1.348 [95% confidence interval (CI), 1.062-1.712] compared with the low N/L ratio group. The average N/L ratio of the 225 patients in the surgery group was 2.79±2.46 (range 0.77-22.75 years). Multivariate analysis revealed that a preoperatively high N/L ratio (P=0.013; HR=2.945; 95% CI, 1.256-6.906) was significantly associated with poor prognosis after bone metastasis in the surgery group. In conclusion, the N/L ratio was confirmed to be an independent prognostic factor in patients with bone metastasis. Thus, the N/L ratio may serve as a clinically accessible and useful biomarker for patient survival.

The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in rectal carcinoma.

OBJECTIVE: In cancer patients, the balance between neutrophil (N) and lymphocyte (L) cell counts fluctuates with advancing disease. The objective of our study was to determine the prognostic implications of the N/L ratio in the peripheral blood of rectal cancer patients. METHODS: Study participants were identified from a prospective cohort of patients with rectal cancer in Dalian of China (n = 123). RESULTS: The median baseline N/L ratio was 2.41 +/- 2.206 (range, 0.76-20.45). Our results revealed that the N/L ratio was significantly associated with tumor size (P = 0.003) and level of cancer antigen 125 (P = 0.027). A multivariate Cox model established a significant relationship between the N/L ratio and survival (adjusted hazard ratio, 2.615; 95% confidence interval, 1.152-5.933; P = 0.021). CONCLUSIONS: These results suggest that the N/L ratio is an independent prognostic factor in rectal cancer, and the N/L ratio may serve as a clinically accessible and useful biomarker for patient survival.

It is possible that tumour-infiltrating granulocytes promote tumour progression.

Several lines of evidence indicate that tumour-infiltrating granulocytes (TIGs) promote tumour growth and progression. However, the prognostic significance of TIGs, the relationship between TIGs and Fas ligand (FasL) expressed on tumour cells remains unclear and warrants investigation. Using immunnostaining, we retrospectively investigated TIGs and FasL in 130 tissue specimens from gastric carcinoma. We analyzed the correlation among these markers, their association with clinicopathologic features and prognosis. The number of TIGs was significantly associated with FasL-expression (P=0.002). Further, TIGs were significantly associated with depth of tumour invasion, lymph node metastasis and tumour stage. Calculating the prognostic relevance, in multivariate analysis, TIGs [relative risk (RR)=1.014; 95% CI=1.002-1.027; P=0.015] and tumour stage were statistically significant factors for survival. Our results suggest that TIGs are conveniently measured by the immunostaining method, and possibly serve as an independent factor of prognosis in patients with gastric carcinoma. This is based on the fact that TIGs were significantly associated with tumour stage and shorter survival time.

The distribution and intracellular location of Fas and Fas Ligand following gastric carcinogenesis: Fas Ligand expressing gastric carcinoma cells can inhibit local immune response.

Previous reports indicated that Fas Ligand (FasL) in gastric carcinoma might support tumour cells to evade host immune attack. However, the mechanism induced by the Fas/FasL system has not yet been described on the basis of comparison of normal and malignant tissues in terms of the features of regional location of Fas and FasL. By using immunostaining methods, we studied the distribution and regional location of Fas and FasL in gastric epithelial cells (GECs), gastric carcinoma cells (GCCs), normal gastric stroma-infiltrating lymphoid cells (NGILs) and tumour-infiltrating lymphoid cells (TILs) in 59 tissue specimens of human gastric carcinoma. The expression of Fas within the entire GECs was higher than that in all GCCs (P < 0.0001); however, the expression of Fas in NGILs was lower than that in TILs (P < 0.0001). The expression of FasL showed no significant difference between GECs and GCCs, or between NGILs and TILs. When we analyzed the Fas/FasL expression on cytomembrane (CM) in GECs and GCCs, Fas-in-CM was detected in 79.4% and 33.33% (P < 0.05), compared with 3.03% and 56.67%, respectively, for FasL-in-CM (P < 0.001). Our results suggest that there is indeed a possible mechanism to assist cancer cells to evade host immune attack, and this mechanism depends on the dynamic state of Fas/FasL expression, that is, Fas showed a tendency to be expressed within the cells, whereas FasL showed a tendency to be expressed on the cell membrane following carcinogenesis.

The granulocyte/lymphocyte ratio as an independent predictor of tumour growth, metastasis and progression: Its clinical applications.

Several investigators have suggested that the granulocyte/lymphocyte (G/L) ratio is a good indicator for the evaluation of the condition of a tumour-bearing host, although its prognotic significance is unclear. To further investigate the clinical applications of the G/L ratio, we injected 1x105 and 1x106 Lewis lung carcinoma cells (3LLc) into the feet of 4-week-old C57BL/6 mice separated into groups A, B, C and D (1x105 cells) and E, F, G and H (1x106 cells). For the observation of tumour metastasis and G/L ratio, the mice in groups A-D were sacrificed on days 11, 14, 17 and 21 after inoculation with the 3LLc cells, and the mice in groups E-H on days 7, 11, 14 and 17. The results suggest that in mice the number of granulocytes increases with time after 3LLc cell injection (P<0.05). We also retrospectively investigated the correlation between G/L ratio, clinicopathologic features and prognosis in 62 patients with gastric carcinoma. There was a significant correlation between the G/L ratio and tumour weight (r=0.746, P<0.05), as well as a significant difference between the G/L ratio and the extent of metastases (P<0.05). Additionally, the G/L ratio was significantly associated with lymph node metastasis and higher tumour stage, tumour progression (P=0.017) and 5-year survival (P=0.013). In conclusion, the G/L ratio is associated with tumour progression and shorter survival. The close correlation between G/L ratio and tumour stage or lymph node status suggests that it could be used to predict tumour metastasis, prognosis and overall survival in patients with gastric carcinoma before they undergo surgical treatment.

Increased density and diameter of lymphatic microvessels correlate with lymph node metastasis in early stage invasive colorectal carcinoma.

To determine whether lymphangiogenesis was associated with the development of colorectal carcinoma and whether the mean maximal diameter of lymphatic microvessels (LMMMD) or lymphatic microvessel density (LMVD) is associated with lymph node metastasis in early stage invasive colorectal carcinoma (T1 carcinoma), we used immunohistochemical staining with podoplanin to measure LMMMD and LMVD in intratumoral (LMMMDit, LMVDit) and peritumoral areas (LMMMDpt, LMVDpt) of T1 carcinomas (n=87). By comparing the LMMMD and LMVD in normal large intestine (n=10), adenoma (n=15), and Tis carcinoma (n=15), we found out that the LMVDpt in T1 carcinoma with lymphatic vessel invasion (LVI) was significantly high (P<0.001), and there was a significant decrease in LMMMDpt in T1 carcinoma (P=0.031). Both LMMMDpt and LMVDpt were significantly increased in the T1 carcinomas, with LVI compared with the T1 carcinomas without LVI (P=0.018, P=0.003). Multivariate analysis revealed that LVI and combined greater LMMMDpt and greater LMVDpt were associated with lymph node metastases (P=0.005, P=0.036). These results indicate that lymphangiogenesis might be induced in the surrounding tumor areas of the T1 colorectal carcinoma with LVI; thus, evaluation of the diameter and density of lymphatic microvessels is important in T1 colorectal carcinoma to predict lymph node metastases.