Comprehensive evaluation of military training-induced fatigue among soldiers in China: A Delphi consensus study.

Objective: Military training-induced fatigue (MIF) often results into non-combat attrition. However, standard evaluation of MIF is unavailable. This study aimed to provide credible suggestions about MIF-evaluation. Methods: A 3-round Delphi study was performed. The authority of the experts was assessed by the authority coefficient (Aa). In round 1, categories of indicators were collected via anonymous survey of experts, then potential indicators were selected via literature search. In round 2, experts should evaluate the clinical implication, practical value, and importance of each potential indicators, or recommend new indicators based on feedback of round 1. Indicators with recommendation proportions ≥ 70% and new recommended indicators would be included in round 3 to be rated on a 5-point Likert scale. "Consensus in" was achieved when coefficient of concordance (Kendall's W) of a round was between 0.2 and 0.5 and the coefficient of variation (CV) of each aspect for an indicator was < 0.5. If round 3 could not achieve "consensus in," more rounds would be conducted iteratively based on round 3. Indicators included in the recommendation set were ultimately classified into grade I (highly recommended) or grade II (recommended) according to the mean score and CV of the aspects. Results: Twenty-three experts participated with credible authority coefficient (mean Aa = 0.733). "Consensus in" was achieved in round 3 (Kendall's W = 0.435, p < 0.001; all CV < 0.5). Round 1 recommended 10 categories with 73 indicators identified from 2,971 articles. After 3-round consultation, consensus was reached on 28 indicators focusing on the cardiovascular system (n = 4), oxygen transport system (n = 5), energy metabolism/metabolite level (n = 6), muscle/tissue damage level (n = 3), neurological function (n = 2), neuropsychological/psychological function (n = 3), endocrine function (n = 3), and exercise capacity (n = 2). Among these, 11 indicators were recommended as grade I: basic heart rate, heart-rate recovery time, heart rate variability, hemoglobin, blood lactic acid, urine protein, creatine kinase, reaction time, Borg Rating of Perceived Exertion Scale, testosterone/cortisol, and vertical jump height. Conclusion: This study developed a reliable foundation for the comprehensive evaluation of MIF among soldiers.

Long non-coding RNA ncRuPAR regulates gastric cancer cell proliferation and apoptosis via phosphoinositide 3-kinase/protein kinase B signaling.

Objective: To determine the effect and mechanism of the long non-coding RNA (lncRNA) ncRuPAR (non-protein coding RNA, upstream of coagulation factor II thrombin receptor [F2R]/protease-activated receptor-1 [PAR-1]) in human gastric cancer. Methods: HGC-27-ncRuPAR overexpression and MGC-803-ncRuPAR-RNAi knockdown gastric cancer cell lines were established. We assessed the effect of ncRuPAR on cell proliferation, apoptosis, migration, and invasion using Cell Counting Kit 8, flow cytometry, scratch and transwell assays, respectively. Differentially expressed genes in HGC-27-ncRuPAR overexpression and HGC-27-empty vector cell lines were identified using Affymetrix GeneChip microarray analysis. Ingenuity Pathway Analysis (IPA) of the microarray results was subsequently conducted to identify ncRuPAR-enriched pathways, followed by validation using real time-quantitative PCR (RT-qPCR). As one of the top enriched pathways, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was further examined by western blotting to determine its role in ncRuPAR-mediated regulation of gastric cancer pathogenesis. Results: ncRuPAR inhibited human gastric cancer cell proliferation and induced G1/S phase arrest and apoptosis, but did not affect migration or invasion in vitro. Overexpression of ncRuPAR in vitro was found to inhibit its known target PAR-1, as well as PI3K/Akt signaling. The downstream targets of PI3K/Akt, cyclin D1 was downregulated, but there was no change in expression level of B-cell lymphoma 2 (Bcl-2). Conclusions: We showed that lncRNA-ncRuPAR could inhibit tumor cell proliferation and promote apoptosis of human gastric cancer cells, potentially by inhibiting PAR-1, PI3K/Akt signaling, and cyclin D1. The results suggest a potential role for lncRNAs as key regulatory hubs in GC progression.

Opposite effect of basic combat training on mood state of recruits with different physical fitness: A study from perspective of fatigue.

Objective: Basic combat training (BCT) is a kind of necessary high-intensity training to help each military recruit convert into a qualified soldier. In China, both the physical fatigue and passive psychological state have been observed in new recruits during BCT. However, after same-intensity training, the degree of fatigue and passive mood vary among recruits. Therefore, this study aimed to explore the effect of BCT on mood state of recruits with different physical fitness levels from a perspective of fatigue. Materials and methods: Before and after BCT, the degree of fatigue and mood state of participants were evaluated via the Borg Rating of Perceived Exertion Scale and Profile of Mood States Questionnaire immediately after 20 push-ups as RPE and POMS scores [total mood disturbance (TMD), passive mood (Ttension, Tanger, Tfatigue, Tdepression, and Tconfusion) and positive mood (Tvigour and Testeem)]. The participants were divided into two groups according to the RPE score measured after BCT: (1) group 1: RPE score after BCT < 13 and (2) group 2: RPE score after BCT ≥ 13. Result: A total of 564 recruits were included (group 1: 456/564, 80.85%; group 2: 108/564, 19.15%). After BCT, in group 1, TMD (from 95.65 ± 17.89 to 87.52 ± 17.63) and passive mood Ttension (from 4.46 ± 3.18 to 3.79 ± 3.14), Tfatigue (from 4.94 ± 3.58 to 3.12 ± 3.04), Tdepression (from 2.86 ± 3.41 to 2.01 ± 2.75), Tconfusion (3.12 ± 2.72 to 2.42 ± 2.57) declined significantly (all within-group p < 0.001), but positive mood both increased significantly (Tvigour: from 13.21 ± 4.59 to 15.44 ± 5.42, Testeem: from 9.18 ± 3.36 to 11.04 ± 3.67; both within-group p < 0.001); while in group 2, only Tanger (from 4.27 ± 4.16 to 6.22 ± 5.94, within-group p = 0.001) and Testeem (from 8.36 ± 3.15 to 9.07 ± 3.67, within-group p = 0.031) increased significantly. Conclusion: BCT could alleviate passive mood and add to positive mood for recruits with better physical fitness, while had no ameliorative effects on or even deteriorate most of the passive mood for recruits with worse physical fitness.

Ziyin Huatan Recipe, a Chinese herbal compound, inhibits migration and invasion of gastric cancer by upregulating RUNX3 expression.

OBJECTIVES: Ziyin Huatan Recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo. METHODS: Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene. RESULTS: The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT. CONCLUSION: ZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.

Mild iron overload induces TRIP12-mediated degradation of YY1 to trigger hepatic inflammation.

Increasing populations are found to bear mild hepatic iron overload (HIO) due to unhealthy lifestyles, metabolic diseases, etc., whether this mild but chronic HIO induces hepatic inflammation is unknown. In the present study, mice receiving a 12-months 0.3% dextran-iron diet show mild HIO with no detectable oxidative damages in the liver but have infiltrated macrophages and increased IL-6, TNFα, AST and ALT since 6-months. The HNF4α/miR-122/CCL2 pathway, identified by our previous studies to induce macrophages infiltration, is initiated by chronic mild HIO. After excluding the role of DNA methylation, a modified transcription factor microarray is applied to find that transcription factor YY1 is responsible for HIO-decreased HNF4α expression. Then the E3 ubiquitin ligase TRIP12 is identified by an immunoprecipitation coupled LC-MS/MS and proved to bind and ubiquitinate YY1, leading to its degradation. The overexpression or silence of YY1 in the liver regulates the HNF4α/miR-122/CCL2 pathway. More importantly, YY1 overexpression alleviates chronic mild HIO induced hepatic inflammatory responses. In conclusion, these results elucidate an oxidative-stress-independent, TRIP12/YY1/HNF4α/miR-122/CCL2 pathway of chronic mild HIO inducing hepatic inflammation, implying that effective measures in addition to antioxidants are needed for individuals at the risk of chronic mild HIO.

ZiYinHuaTan Recipe Inhibits Cell Proliferation and Promotes Apoptosis in Gastric Cancer by Suppressing PI3K/AKT Pathway.

In recent years, traditional Chinese medicine has played an important role in the treatment of gastric cancer in China. ZiYinHuaTan (ZYHT) recipe was developed for advanced gastric cancer and had shown its promising value in the clinic. In this study, we explore the effect of ZYHT on gastric cancer in vitro and in vivo. ZYHT can inhibit tumor growth and improve the general condition of mice in subcutaneous transplantation nude mice models of gastric cancer. And ZYHT can also inhibit cell proliferation and blocked the cells in G0/G1 to induce cell apoptosis in HGC27 and MGC803 cells. Then, network pharmacology analysis showed that ZYHT may exert antitumor effect mainly through PI3K/AKT signaling pathway. Furthermore, the expression of PI3K, p-Akt, CyclinD1, and Bcl-2 was detected in vitro and in vivo. The results showed that ZYHT could decrease the expression of PI3K, CyclinD1, and Bcl-2 both in vitro and in vivo. These results suggested that ZYHT could be used as a method for the treatment of developed gastric cancer.

Ameliorative effects of Tai Chi on cancer-related fatigue: a meta-analysis of randomized controlled trials.

PURPOSE: This meta-analysis investigated the effectiveness of Tai Chi on cancer-related fatigue (CRF). METHODS: Nine databases (PubMed, Web of Science, Ovid, the Cochrane Library, Embase, and four Chinese databases) were searched to identify randomized controlled trials (RCTs) that evaluated the effects of Tai Chi on CRF. The reference lists given in the identified RCTs were also reviewed to identify potentially relevant studies. RESULTS: Six RCTs involving 373 patients were included. The change in short- and long-term CRF (SCRF and LCRF, respectively) was calculated as the change in the mean score for CRF from baseline to the end of intervention period and to the end of post-intervention follow-up, respectively. Pooled results suggested that Tai Chi had a significant positive effect on standard mean difference (i.e., SCRF; SMD = - 0.54; p < 0.0001), but the impact on LCRF remained unclear. Subgroup analyses of SCRF indicated positive effects of Tai Chi among patients with breast (SMD = - 0.81; p < 0.00001) and lung cancer (SMD = - 0.50; p = 0.002), but not prostate cancer (p = 0.98). Tai Chi also had effects on SCRF that were superior to physical exercise and psychological support (SMD = - 0.49 and - 0.84, respectively; both p < 0.05). A longer intervention time (8-12 weeks) benefited SCRF more than a shorter time (SMD = - 1.08 and - 0.36, respectively; both p < 0.05). CONCLUSION: Tai Chi for more than 8 weeks has short-term ameliorative effects on CRF, especially among patients with breast and lung cancer. Its beneficial effects are superior to physical exercise and psychological support. It remains unclear whether there are long-term benefits, and further study is needed.

Protease-activated receptor-1 (PAR-1): a promising molecular target for cancer.

PAR-1 is expressed not only in epithelium, neurons, astrocytes, immune cells, but also in cancer-associated fibroblasts, ECs (epithelial cells), myocytes of blood vessels, mast cells, and macrophages in tumor microenvironment, whereas PAR-1 stimulates macrophages to synthesize and secrete thrombin as well as other growth factors, resulting in enhanced cell proliferation, tumor growth and metastasis. Therefore, considerable effort has been devoted to the development of inhibitors targeting PAR-1. Here, we provide a comprehensive review of PAR-1's role in cancer invasiveness and dissemination, as well as potential therapeutic strategies targeting PAR-1 signaling.