Search

To investigate the correlation of platelet and coagulation function with blood stasis syndrome (BSS) in coronary heart disease (CHD). The protocol for this meta-analysis was registered on PROSPERO (CRD42019129452). PubMed, Excerpta Medica Database (Embase), the Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched from inception to 1st June, 2020. Trials were considered eligible if they enrolled BSS and non-BSS (NBSS) patients with CHD and provided information on platelet and coagulation function. The platelet function, coagulation function, and fibrinolytic activity were compared between the BSS and NBSS groups. Forest plots were generated to show the SMDs or ESs with corresponding 95% CIs for each study. Subgroup analysis and sensitivity analysis were performed to explore potential sources of heterogeneity. The systematic search identified 1,583 articles. Thirty trials involving 10,323 patients were included in the meta-analysis. The results showed that mean platelet volume, platelet distribution width, platelet aggregation rate, platelet P selectin, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), thromboxane B2 (TXB2), 6-keto-prostaglandin F1alpha (6-keto-PGF1 α), and TXB2/6-keto-PGF1 α were higher in the BSS group than in the NBSS group (P

Gastric cancer accounts for the majority cancer-related deaths worldwide. Although various methods have considerably improved the screening, diagnosis, and treatment of gastric cancer, its incidence is still high in Asia, and the 5-year survival rate of advanced gastric cancer patients is only 10%-20%. Therefore, more effective drugs and better screening strategies are needed for reducing the incidence and mortality of gastric cancer. Cyclooxygenase-2 (COX-2) is considered to be the key inducible enzyme in prostaglandins (PGs) synthesis, which is involved in multiple pathways in the inflammatory response. For example, inflammatory cytokines stimulate innate immune responses via Toll-like receptors and nuclear factor-kappa B to induce COX-2/PGE2 pathway. In these processes, the production of an inflammatory microenvironment promotes the occurrence of gastric cancer. Epidemiological studies have also indicated that non-steroidal anti-inflammatory drugs can reduce the risk of malignant tumors of the digestive system by blocking the effect of COX-2. However, clinical use of COX-2 inhibitors to prevent or treat gastric cancer may be limited because of potential side effects, especially in the cardiovascular system. Given these side effects and low treatment efficacy, new therapeutic approaches and early screening strategies are urgently needed. Some studies have shown that genetic variation in COX-2 also play an important role in carcinogenesis. However, the genetic variation analysis in these studies is incomplete and isolated, pointing out only a few single nucleotide polymorphisms (SNPs) and the risk of gastric cancer, and no comprehensive study covering the whole gene region has been carried out. In addition, copy number variation (CNV) is not mentioned. In this review, we summarize the SNPs in the whole COX-2 gene sequence, including exons, introns, and both the 5’ and 3’ untranslated regions. Results suggest that COX-2 does not increase its expression through the CNV and the SNPs in COX-2 may serve as the potential marker to establish risk stratification in the general population. This review synthesizes emerging insights of COX-2 as a biomarker in multiple studies, summarizes the association between whole COX-2 sequence variation and susceptibility to gastric cancer, and discusses the future prospect of therapeutic intervention, which will be helpful for early screening and further research to find new approaches to gastric cancer treatment.

The coronavirus disease 2019 (COVID-19) has been spreading worldwide, posing a significant threat to human health. Currently, vaccines are available, but there is still no reliable cure for this disease. Traditional Chinese Medicine (TCM) has played an important role in addressing this epidemic, and several clinical studies have emerged regarding treatments for COVID-19 by TCM; status of those treatments, and patterns regarding these are worth summarizing and interpreting systematically. A comprehensive search of clinical trials was performed in various platforms, including PubMed, Embase, Web of Science, medRxiv, China National Knowledge Infrastructure, WanFang Data, and SinoMed, from January 1, 2020 to March 1, 2021. Analyzed information included language, received date, quantity, citations, affiliation, number of authors, research type (randomized controlled trial or non-randomized controlled trial), trial registry information, disease severity, sample size, specific interventions, outcomes, and adverse reactions, among others. Based on the aforementioned information, a quantitative and qualitative literature analysis was done. A total of 47 articles were retrieved, most of which were published in Chinese (42 articles, 89.36%). Based on the results of the number of trial registrations (12 articles), the number of citations (the maximum for a single article was 62), and the modified Chalmers scale (total: 100 points, average: 61.40 points), the overall study quality still needs improvement. Most patients presented with the mild and common type of COVID-19 and were recruited in Hubei Province, while researchers from these studies were from all over the country (135 institutions). TCM interventions included 66 different formulas and 134 herbs, of which Armeniacae semen amarum (Kuxingren), Agastache rugosa (Huoxiang), Ephedra sinica stapf (Mahuang), Gypsum fibrosum (Shigao), Glycyrrhizae radix et rhizome (Gancao), and Gtractylodes rhizoma (Cangzhu) appeared at high frequencies. Highlighted outcomes from these studies included the following: Clinical symptoms (fever, cough, fatigue, etc.), progression rate from normal stage to heavy stage, laboratory indices including leukocyte and lymphocyte counts, and c-reactive protein levels, imaging diversity of lung computed tomography (CT), and recorded adverse reactions. With a certain number of published clinical trials, the landscape of TCM clinical trials for COVID-19 was established. Most studies have a relatively low quality and impact, and standardized implementation of evidence-based research in TCM was lacking. The mainstay TCM treatment for COVID-19 involved clearing heat, releasing the exterior, and resolving its dampness. Additionally, the Maxing Shigan Decoction was one of the most common classical prescriptions for COVID-19, and the “three drugs and three perceptions” were also widely used. Some symptoms, laboratory indicators, and imaging diversity of lung CT were found to have significantly improved after taking these decoctions. Overall, TCM is safe, and no serious adverse reactions have been reported. Through multiple mechanisms, TCM has shown great clinical effects, but its underlying mechanisms and patterns should be further explored. It is of great practical significance to enhance the level of clinical and evidence-based research for TCM application in the prevention and treatment of acute and emergent infectious diseases. Furthermore, such research will help strengthen clinical expertise in this field and further standardize the implementation of evidence-based TCM medical research.

Di(2-ethylhexyl) phthalate (DEHP), as an endocrine disruptor, is often used as a plasticizer in various polyvinyl chloride plastic products and medical consumables. Epidemiological studies have shown that long-term large intake of DEHP may be a risk factor for liver dysfunction. Long-term exposure to DEHP is associated with liver disease and aggravates the progression of chronic liver injury. However, the effects of DEHP on hepatocellular carcinoma (HCC) are rarely studied. In this study, we sought to determine the effects of DEHP on HCC induced by carbon tetrachloride combined with diethylnitrosamine, and further study its molecular mechanism. It was found that DEHP exposure significantly promotes tumor immune escape and activates signaling pathways involved in related protein expression of tumor immune escape, including PD-L1, JAK2, and STAT3. In addition, the trends observed in the HepG2 cells assay are consistent with vivo conditions. In summary, DEHP may play a tumor-promoting role in HCC mice and IFN-γ stimulated HepG2 cells, which may be related to the JAK2/STAT3 signaling pathway.

Background: Kiss1, also known as Kisspeptin-1 and metastin, is a protein coded by the KISS1 gene (1). The receptor for KISS1, KISS1R (also known as G-protein coupled receptor 54 or GPR54 is coded by the KISS1R gene. Kiss1 and Kiss1R have been indicated in a number of pathophysiological conditions, including metabolic and reproductive abnormalities and the protein complex has been well indicated in the development and progression of a number of solid cancers including the metastatic potential of cancer cells (1) and in clinical cancers including breast cancer (2). Here, the intracellular events associated with KISS1/KISS1R signalling have been explored, including focal adhesion kinase and phospholipase-C (PLC) pathways where we employed a protein kinase platform together with a clinical breast cohort in order to explore protein kinases that are involved in KISS1 signalling and the clinical significance. Methods: A protein kinase microarray (Kinexus850) was employed to detect the cellular kinase responses to exogenous Kisspeptin stimulation. Kiss1, Kiss1 receptor (KISS1R or GPR54) and the prospective members of the protein kinase C (PKC) family members were assessed for the expression in a Cardiff breast cancer cohort and were analysed against the pathological and clinical outcomes of the patients. Results. Using the Kinexus protein kinase platform, we identified that some key members of the protein kinase C family were upregulated in response to treatment with exogenous Kisspeptin. These members include Protein kinase C (PKC)-gamma, PKC-iota, PKC-zeta and PKC-delta, which are potential downsteam targets of KISS1/KISS1R. In our clinical cohort, KISS1 was significantly correlated with the expression levels of PKC-iota (p=0.01) and PKC-gamma (p References 1. Lee JH, Miele ME, Hicks DJ, Phillips KK, Trent JM, Weissman BE, Welch DR. KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst. 1996, 88:1731-7. 2. Tracey A Martin 1, Gareth Watkins, Wen G Jiang. KiSS-1 Expression in Human Breast Cancer. Clin Exp Metastasis, 2005;22:503-11 Citation Format: Tracey Amanda Martin, Edison Ke Ji, Amy G Jiang, Rishana Thayaparan, Robert E Mansel, Eleri Davies, Wen G Jiang. Kiss1, the kiss1 receptor (kiss1r) and the protein kinase c (pkc) family identifies patients with clinical outcome in clinical breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-42.

The long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) has been implicated in many tumors risk including gastric cancer. However, the association of single nucleotide polymorphisms (SNPs) at NEAT1 with gastric cancer risk has not been studied. The aim of this study was to investigate the association between SNPs in NEAT1 and gastric cancer susceptibility. In this study, four SNPs in lncRNA NEAT1 were selected for genotyping in 484 gastric cancer patients and 484 controls in Chinese Han population. Quantitative real-time PCR (qRT-PCR) was conducted to evaluate the potential function of rs3825071. Attributable risk percentage (ARP) and population attributable risk percentage (PARP) were used to assess the epidemiological effect. In the dominant model (GG), the genotypes AG + AA of rs3825071 and rs7943779 were associated with an increased risk of gastric cancer (OR = 1.72, 95%CI = 1.27–2.32 and OR = 1.63, 95%CI = 1.19–2.22). Individuals harboring ≥ 3 risk alleles have higher risk of gastric cancer (OR = 1.88, 95% CI = 1.26–2.80, P = 0.002). ARP and PARP associated with gastric cancer were 42.53% and 10.88% for rs3825071, and were 33.78% and 6.26% for rs7943779, respectively. Furthermore, compared with the genotype GG of rs3825071, the genotypes AG and AA had higher expression of NEAT1. We found that the genetic variations in NEAT1 were significantly associated with risk of gastric cancer. The G > A variant of rs3825071 may confer gastric cancer susceptibility by changed biological effects to increase the expression of NEAT1.

To reveal the underlying relationships between Chinese medicine (CM) syndromes and ultrafiltration (UF) in the treatment of heart failure based on a metabonomic approach. Seventeen acute decompensated heart failure (ADHF) patients were enrolled, and their CM syndromes before and after UF were collected. In addition, their venous plasma collected before and after UF was used for liquid chromatographmass spectrometer-based metabonomic analysis. Both reversed phase liquid chromatography and hydrophilic interaction liquid chromatography were used to analyze the plasma samples. Partial least-squares to latent structure-discriminant analyses were used for data analysis. An obvious difference was observed pre- and post-treatment. A total of 17 potential biomarkers associating with alterd syndromes with UF including hypoxanthine, 1-methylhistidine, phytosphingosine, O-decanoyl-R-carnitine, etc. were screened out, showing a significant change after UF. The major adjusted metabolic pathways were purine metabolism, histidine metabolism, leucine and isoleucine metabolism, arginine and proline metabolism, carnitine shuttle, sphingolipid metabolism and phospholipid metabolism. Metabonomic approach is a useful tool to identify potential biomarkers of altered syndromes link to UF and could provide a theoretical basis for further research on the therapeutic mechanism of UF combined with CM.

Objective This prospective cohort study explored factors related to postoperative pain in gastric cancer patients. Methods A total of 236 patients who underwent gastrectomy were enrolled. All patients enrolled in the study completed the Hospital Anxiety and Depression Scale (HADS) questionnaire and Life Orientation Test-Revised (LOT-R) questionnaire on the day before surgery. Heat pain threshold (HPT), cold pain threshold (CPT) and pressure pain threshold (PPT) were measured for all patients one day prior to surgery and demographic details were collected. All patients were connected to a patient-controlled intravenous analgesia (PCIA) pump at the end of the surgery. The occurrence of postoperative pain was used as a dependent variable, and multivariate logistic regression analyses were conducted to screen for factors affecting postoperative pain. Results In total, 83 patients (35.2%) had postoperative pain. Body mass index (BMI) ≥28 kg/m2 [odds ratio (OR): 2.67; 95% confidence interval (95% CI): 1.07-6.67], total gastrectomy (OR: 2.64; 95% CI: 1.42-4.91), preoperative anxiety score ≥8 (OR: 2.37; 95% CI: 1.12-5.02), heat pain threshold ≤4.9 s (OR: 2.14; 95% CI: 1.06-4.32), pressure pain threshold ≤4 g (OR: 2.05; 95% CI: 1.05-4.03), and female gender (OR: 1.99; 95% CI: 1.04-3.83) were risk factors for postoperative pain. Conclusions Obesity, wide range of gastrectomy, high preoperative anxiety, low HPT and PPT, and female gender are associated with increased risk for postoperative pain.

Purpose The aim of the present study was to compare the difference between double tract reconstruction and esophagogastrostomy.Materials and Methods Patients who underwent radical proximal gastrectomy with esophagogastrostomy or double tract reconstruction were included in this study.Results Sixty-four patients were included in this study and divided into two groups according to reconstruction method. The two groups were well balanced in perioperative safety and 3-year overall survival (OS). The rates of postoperative reflux esophagitis in the double tract reconstruction group and esophagogastrostomy group were 8.0% and 30.8%, respectively (p=0.032). Patients in the double tract reconstruction group had a better global health status (p < 0.001) and emotional functioning (p < 0.001), and complained less about nausea and vomiting (p < 0.001), pain (p=0.039), insomnia (p=0.003), and appetite loss (p < 0.001) based on the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. Regarding the EORTC QLQ-STO22 questionnaire, patients in the double tract reconstruction group complained less about dysphagia (p=0.030), pain (p=0.008), reflux (p < 0.001), eating (p < 0.001), anxiety (p < 0.001), dry mouth (p=0.007), and taste (p=0.001). The multiple linear regression analysis showed that reconstruction method, postoperative complications, reflux esophagitis, and operation duration had a linear relationship with the global health status score.Conclusion Double tract reconstruction could better prevent reflux esophagitis and improve quality of life without scarifying perioperative safety or 3-year OS.

Background Positive peritoneal cytology (PCY) indicates metastasis (M1) in gastric cancer (GC) patients; both the American and Chinese guidelines recommend laparoscopic peritoneal lavage (LPL) for cytology. However, relatively high costs impair the widespread use of LPL in some resource‐limited regions in China, and the cost‐effectiveness of PCY testing remains unclear. Therefore, we performed a decision analysis to evaluate the cost‐effectiveness of PCY testing by comparing the guideline‐recommended intraoperative LPL, a newly proposed preoperative percutaneous peritoneal lavage (PPL), and a third strategy of exploratory laparotomy with no cytology testing (ELNC) among GC patients. Methods We developed a decision‐analytic Markov model of the aforementioned three strategies for a hypothetical cohort of GC patients with curative intent after initial imaging, from the perspective of Chinese society. We estimated costs, quality‐adjusted life years (QALYs), and incremental cost‐effectiveness ratios (ICERs) as primary outcomes; we also conducted one‐way and probabilistic sensitivity analyses to investigate the model's robustness. Results We found that ELNC was dominated (i.e., more expensive and less effective) by PPL and LPL. LPL was the most cost‐effective method with an ICER of US$17,200/QALY compared to PPL, which was below the Chinese willingness‐to‐pay (WTP) threshold of US$29,313 per QALY gained. In sensitivity analyses, PPL was more likely to be cost‐effective with a lower WTP threshold. Conclusions Cytology testing through either LPL or PPL was less expensive and more effective than ELNC among GC patients. Moreover, LPL was the most cost‐effective modality at the current WTP threshold, while PPL could potentially be cost‐effective in lower‐income areas., This is the first decision analysis evaluating the cost‐effectiveness of peritoneal cytology tests among gastric cancer patients. We found performing cytology testing during the gastric cancer staging dominated (i.e., less expensive and more effective) no cytology testing among patients with curative intent, and the guideline‐recommended laparoscopy with cytology was the most cost‐effective modality at the current willing‐to‐pay threshold in China.

Background Encrusted cystitis (EC) is a chronic inflammation of the bladder associated with mucosal encrustations. Early diagnosis and optimal treatment are not well established. Here, we report a case of EC successfully treated with com-bination therapy. Case summary A 27-year-old man presented with frequency, urgency, dysuria, gross hematuria and suprapubic pain for 2 mo. He was diagnosed with EC based on characteristic calcifications of the bladder wall (most of them were struvite), cystoscopy and histopathological examination. He was cured after combined therapy of elimination of encrustations, bladder instillation of hyaluronic acid and injection of botulinum-A neurotoxin into bladder submucosal tissue. Conclusion Bladder instillation of hyaluronic acid and injection of botulinum-A neurotoxin into the bladder submucosal tissue can be used for treatment of EC.

The incidence of cognitive impairment (CI) is gradually increasing, which has attracted more attention from medical researchers worldwide. Definitive mechanisms of pathogenesis remain elusive, and there are few medications that have been proven effective for CI. The utilization of Chinese herbal medicine has shown positive therapeutic effects for a broad spectrum of diseases, including CI. The purpose of this study is to evaluate the safety and efficacy of Guilingji Capsules (GLJC,龟龄集 胶囊) in treating mild-to-moderate CI with Shen (Kidney) and marrow deficiency syndrome. This is a randomized, double-blind, positive-controlled, multicenter clinical trial with a noninferiority design that included 348 participants randomly divided into an experimental arm and an active comparator arm. Individuals in the experimental arm (174 cases) took 0.6 g of GLJC once a day and 19.2 mg of Gingko biloba extract mimetic 3 times a day. Individuals in the active comparator arm (174 cases) took 0.6 g of GLJC mimetic once a day and 19.2 mg of Gingko biloba extract in tablet form 3 times a day. The intervention period included two sessions over 24 weeks. The primary outcome be the effectiveness of GLJC on cognitive improvement after 24 weeks of treatment, which was defined as an increase in the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) Scale. The secondary outcomes were improvement in independence, daily living ability, and Chinese medicine (CM) syndrome, which were measured with the Alzheimer's disease Rating Scale-Cognitive Project (ADAS-Cog), Clinical Dementia Rating (CDR) Total Score, Activities of Daily Living (ADL) Total Score and the Chinese Medicine Symptom Scale (CM-SS), respectively. Serum acetylcholine, acetylcholinesterase, bax and bcl-2 were monitored to explore the mechanism of GLJC on CI. In addition, safety measures, including vital signs, electrocardiography, laboratory indicators (full blood count, kidney and liver function tests, routine urine test and routine stool test) and adverse events, were also recorded. The purpose of this trial is to evaluate the efficacy and safety of GLJC in patients with mild-to-moderate CI with kidney and marrow deficiency syndrome. If successful, the results would provide a viable treatment for patients with mild-to-moderate CI. (Clinical Trials.gov. ID: NCT03647384. Registered on 23 August 2018)

Amplicon-based next generation sequencing (NGS) approaches have been preferentially adopted by the clinical laboratories on the basis of a short turnaround time (TAT) and small DNA input needs. However, little work has been done to assess the amplicon-based NGS methods for copy number variation (CNV) detection in comparison with current standard methods like immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). The correlation between NGS based CNV detection and the later standard methods has remained unexplored. We developed an amplicon-based panel to detect human epidermal receptor growth factor (HER2) amplification in formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 280 breast cancer and 50 gastric cancer patients. Assessment by IHC and FISH was conducted in parallel, and descriptive statistics were used to assess the concordance. The copy number detected by NGS was correlated with either the average HER2 copy number (signals/cell) (r = 0.844; p

Objective To reveal the distribution signature of cancer susceptibility genes in patients with gastric adenocarcinoma, offering a diagnostic and prognostic surrogate for disease risk management and therapeutic decisions. Methods A total of 282 patients with gastric adenocarcinoma (182 males and 100 females) were enrolled in this study, with peripheral blood genomic DNA extracted. Mutations of 69 canonical cancer susceptibility genes or presumably tumor-related genes were analyzed by targeted capture-based high-throughput sequencing. Candidate mutations were particularly selected for discussion on tumor pathogenesis according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Results In this study, 7.1% (20/282) of patients with gastric adenocarcinoma were found to harbor mutations of canonical or presumable cancer susceptibility genes. The detection rate in male patients (3.8%, 7/182) was significantly lower than that in female patients (13%, 13/100) (P=0.004). The most recurrent mutations were in A-T mutated (ATM) (1.1%, 3/282), followed by BRCA1, BRIP1 and RAD51D, all showed a detection rate of 0.7% (2/282). Mutations in three genes associated with hereditary gastric cancer syndromes were detected, namely, PMS2 and EPCAM associated with Lynch syndrome and CDH1 associated with hereditary diffuse gastric cancer. The detection frequencies were all 0.4% (1/282). Notwithstanding no significant difference observed, the age of patients with pathogenic mutations or likely pathogenic mutations is slightly younger than that of non-carriers (median age: 58.5 vs. 60.5 years old), while the age of patients with ATM mutations was the youngest overall (median age: 49.3 years old). Conclusions Our study shed more light on the distribution signature and pathogenesis of mutations in gastric cancer susceptibility genes, and found the detection rate of pathogenic and likely pathogenic mutations in male patients was significantly lower than that in female patients. Some known and unidentified mutations were found in gastric cancer, which allowed us to gain more insight into the hereditary gastric cancer syndromes from the molecular perspective.

Rationale: Multiple gastric cancer (MGC) is characterized by the presence of more than two different tumors in the stomach. However, the clonal relationship and carcinogenesis of MGC remain unclear. We investigated the clonal relationship and role of germline mutations in the carcinogenesis of MGC. Methods: We gathered 16 multiple gastric cancer patients. Thirty-three tumor samples and sixteen normal gastric tissue or blood samples were obtained from January 2016 to December 2017. We also conducted analyses for 208 gastric cancer and 49 esophagogastric junction cancer (GC-EGJ) tumors from TCGA. DNA extraction from our samples was conducted for whole-exome sequencing (WES). Results: Tumor mutation burden (TMB) was not statistically significant within database and our data in the GC-EGJ (P=0.0591) and GC groups (P=0.3113). The mutation spectrum and signatures also showed uniform distributions in GC and GC-EGJ groups within our data and TCGA database. Among sixteen patients, four were identified as monoclonal, in which 11, 10, 26 and 6 somatic mutations were shared within different tumors of P7, P8, P9 and P16, respectively. However, no common mutation between different tumors of the same patient was found among the other 12 patients. After identifying predisposing genes, we found that germline MSH2 and NCOR2 mutations were significantly dominant in 8/12 and 10/12 of genetic MGC patients. Additionally, all patients were identified with MSH2 mutations in cancer samples of those genetic MGC patients. Taking genetic MGCs as a whole, we identified that TP53 were significantly mutated in 14 of 25 tumor samples. Main conclusions: WES analyses are suggestive of monoclonal and polyclonal origin of MGC, which may promote the classification of MGC into genetic and metastatic MGC. For patients with genetic MGC, germline MSH2 X314_splice variants may contribute to carcinogenesis, thus prompting the consideration of more radical surgery and/or anti-PD-1/PD-L1 therapy.

To elevate the effects of Qingxuan Jiangya Decoction (清眩降压汤, QXJYD) on hypertension and vascular structural remodeling (VSR) in spontaneously hypertensive rats (SHRs), and investigate the underlying mechanisms. SHRs (n=8) were given intra-gastric administration with 60 mg/kg of QXJYD or saline, daily for 8 weeks, while rats in SHR-control (n=8) and WKY (n=8) groups were received equal volumes of saline solution. Systolic blood pressures (SBP), diastolic blood pressures (DBP) and mean blood pressures (MBP) were measured once a week. The levels of angiotensin II (Ang II), endothelin 1 (ET-1) and plasma renin activity (PRA) were tested by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay, respectively. The effect of QXJYD on VSR was determined by examining the media thickness and the ex vivo contractility of thoracic aortic. The proliferation and fibrosis of vascular smooth muscle cells (VSMCs) were examined via immunohistochemical (IHC) staining for proliferating cell nuclear antigen (PCNA), collagen I and collagen III, respectively. The mRNA and protein expressions of transforming growth factor β 1 (TGF-β 1), Smad3 and phosphorylation of Smad3 in thoracic aorta tissues were determined by real-time polymerase chain reaction (PCR) and Western blot assay, respectively. QXJYD treatment led to a significant decrease of the elevation of blood pressure in SHRs and reduced the levels of Ang II, ET-1 and PRA in the serum (P

Exosome, is identified as a nature nanocarrier and intercellular messenger that regulates cell to cell communication. Autophagy is critical in maintenance of protein homeostasis by degradation of damaged proteins and organelles. Autophagy and exosomes take pivotal roles in cellular homeostasis and cardiovascular disease. Currently, the coordinated mechanisms for exosomes and autophagy in the maintenance of cellular fitness are now garnering much attention. In the present review, we discussed the interplay of exosomes and autophagy in the context of physiology and pathology of the heart, which might provide novel insights for diagnostic and therapeutic application of cardiovascular diseases.

Dietary administration of some plant-derived substances have been proved of great economic value in aquaculture. In order to investigate the effects of dietary fenugreek seed extracts (FSE) on juvenile blunt snout bream (Megalobrama amblycephala), a feeding trial was conducted for 8 weeks. The results showed that final weight (FW), weight gain (WG), feed conversion ratio (FCR) and specific growth rate (SGR) were not significantly affected by dietary FSE levels. The whole body lipid contents of fish fed with 0.04%, 0.08% and 0.16% FSE diets were significantly lowered compared to the control group. Dietary FSE diets significantly affected plasma complement component 3 (C3), immunoglobulin M (IgM), albumin (ALB) and total protein (TP). The relative expressions of acetyl CoA carboxylase (ACC), fatty acid synthase (FAS) and sterol regulatory element binding protein-1 (SREBP1) mRNA in the liver of fish decreased significantly with increasing dietary FSE levels from 0% up to 0.04%. FSE supplementation diets lowered the liver pro-inflammatory genes expressions by regulating tumor necrosis factor-α (TNF-α) and interleukin 8 (IL-8) mRNA levels and increased anti-inflammatory genes expression by regulating transforming growth factor (TGF-β) and interleukin 10 (IL-10). FSE diets increased growth factor-1 (IGF-1) and target of rapamycin (TOR) mRNA levels from 0% up to 0.04%, 0.04% FSE diets significantly increased growth factor-1 (IGF-1) mRNA levels and S6 kinase-polypeptide 1 (S6K1) mRNA levels compared to the control group. 0.04% FSE diets significantly increased superoxide dismutase (SOD) activities and 0.08% FSE diets significantly increased catalase (CAT) and glutathione peroxidase (GPx) activities, 0.16% FSE diets significantly increased total antioxidant capacity (T-AOC) activities compared to the control group. Additionally, compared to the control group, 0.04% dietary FSE significantly up-regulated nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA levels and glutathione peroxidase-1 (GPx1) mRNA levels, at the same time, 0.02%, 0.04%, 0.08%, 0.16% FSE diets significantly down-regulated kelch-like ECH-associated protein 1 (Keap1) mRNA levels. However, no significant effects were observed on copper zinc superoxide dismutase (Cu/Zn-SOD) and manganese superoxide dismutase (Mn-SOD). Our study indicated that dietary FSE could improve plasma biochemical parameters, regulate lipid metabolism related genes, promote Nrf2 antioxidant capacity and enhance immune response of juvenile blunt snout bream.

Four diets were formulated with or without fishmeal (FM) and essential amino acid (EAA) supplementation fed to the blunt snout bream throughout 8 weeks. The results showed that total cholesterol level (TC) was decreased significantly against FM reduction (P 0.05). Catalase (CAT) activity and glutathione (GSH) content were significantly augmented and diminished in the group fed diet 3 respectively (P 0.05). Glutathione peroxidase (GPx) activity was elevated significantly either by reducing FM or supplementing EAA (P 0.05), whereas the relative expression of copper-zinc superoxide dismutase (Cu/Zn-SOD) decreased against FM reduction (P < 0.05). The relative expressions of Interleukin 8 (IL-8), tumour necrosis factor-α (TNF-α), interleukin 10 (IL10), and nuclear factor-kappa B (NF-κB) were diminished significantly in FM-reduced groups (P < 0.05). The supplementation of EAA significantly increased the relative expression of signal transducer and activator of transcription 4 (STAT4) (P < 0.05). In conclusion, the results revealed that dietary plant proteins with EAA supplementation significantly affected the physiological status and immune responses in blunt snout bream.

Dietary administration of tryptophan has been proved improving growth performance of fish. An 8-week feeding trial was conducted to investigate the effects of dietary tryptophan level on antioxidant capacity and immune response through Nrf2 and TOR signaling pathway. The results showed that, 0.08% tryptophan level significantly increased plasma aspartate aminotransferase (AST), while immunoglobulin M (IgM) and alkaline phosphatase (ALP) were strikingly increased by 0.40% level. The level of plasma complement component 3 (C3), alanine aminotransferase (ALT) and albumin (ALB) were independent of tryptophan supplementation. Total superoxide dismutase (T-SOD), catalase (CAT), total antioxidant capacity (T-AOC) and glutathione (GSH) activity were increased with increasing dietary tryptophan level until 0.40% and then decreased, while the level of malondialdehyde (MDA) showed a reverse trend. 0.19% and 0.28% tryptophan level significantly improved the glutathione peroxidase 1 (GPx-1) activity. Compared with 0.08% dietary tryptophan level, 0.40% level significantly improved nuclear factor erythroid 2-related factor 2 (Nrf2), GPx, manganese superoxide dismutase (Mn-SOD), CAT and transforming growth factor-β (TGF-β) mRNA level, while Kelch-like ECH-associated protein 1 (Keap1) and interleukin 1β (IL-1β) mRNA level were significantly decreased. The relative expression of copper zinc superoxide dismutase (Cu/Zn-SOD), heme oxygenase-1 (HO-1), target of rapamycin (TOR), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), protein kinase B (Akt) and interleukin 10 (IL-10) were significantly improved by 0.28% diet, while the mRNA level of tumor necrosis factor-α (TNF-α) and nuclear factor-kappa B (NF-κB) were increased by 0.08% diet. Interleukin 8 (IL-8) mRNA level was not significantly affected by dietary tryptophan. Based on MDA and T-SOD value, the optimal dietary tryptophan level of juvenile blunt snout bream was determined to be 0.33% (1.03% of dietary protein) and 0.36% (1.13% of dietary protein), respectively, using quadratic regression analysis.

Background: Type 2 Diabetes mellitus (T2DM) is a major risk factor for cardiovascular diseases and increase mortality. Clinical outcomes of patients after percutaneous coronary intervention (PCI) were worse in T2DM patients than those without T2DM. New-onset diabetes after PCI (NODAP) is often observed during long-term follow-up and this further aggravates cardiovascular diseases. Several studies had focused on patients after PCI with known T2DM. Previous studies showed that impaired glucose tolerance and aging are risk factors that promote NODAP. Considering the unique characteristics of patients after PCI, we will further study relevant risk factors. We sought to investigate the potential predictors of acute coronary syndrome patients with NODAP by a multicenter retrospective cohort study.Methods: This is a multicenter retrospective cohort study including patients after PCI. Clinical medical records of these patients were collected from four hospitals in different areas in China, from 2010 to 2021. Patients' demographic information, medical history, diagnostic testing, PCI-related information, medication situation will be summarized using descriptive statistics, and correlation analysis was performed on the development of new-onset diabetes. Variation will be described and evaluated using χ2 test or Kreskas-Wallis test. The prediction model will be verified by a validation set.Discussion: A novel diabetes prediction model for patients after PCI is established, and this study can achieve advanced intervention for the occurrence of NODAP. Owing to its retrospective nature, this study has some limitations, but it will be further studied through supplement data collection or prospective study. The study has been registered for clinical trials by the Chinese Clinical Trial Registry (ChiCTR2100047241).

Interactions between colonizing microbiota and the host have been fully confirmed, among which the tongue-coating microbiota have a moderate rate of renewal and disease sensitivity and are easily obtained, making them an ideal research subject. Oral microbiota disorders are related to diabetes, obesity, cardiovascular disease, cancer, and other systemic diseases. As an important part of the oral cavity, tongue-coating microbiota can promote gastritis and digestive system tumors, affecting the occurrence and development of multiple chronic diseases. Common risk factors include diet, age, and immune status, among others. Metabolic regulatory mechanisms may be similar between the tongue and gut microbiota. Tongue-coating microbiota can be transferred to the respiratory or digestive tract and create a new balance with local microorganisms, together with the host epithelial cells forming a biological barrier. This barrier is involved in the production and circulation of nitric oxide (NO) and the function of taste receptors, forming the oral-gut-brain axis (similar to the gut-brain axis). At present, the disease model and mechanism of tongue-coating microbiota affecting metabolism have not been widely studied, but they have tremendous potential.

Kidins220 is a transmembrane scaffold protein involved in several types of cancer. The aim of the present study was to examine the role of Kidins220 in tumorigenesis and disease progression of pancreatic cancer. The relevant signalling pathways including EGFR, EMT, and MMP were also investigated. The expression of Kidins220 was examined at the transcript and protein level. The Kidins220 knockdown cell model was established and its influence on cellular functions was determined. Involvement of Kidins220 in tumorigenesis and metastasis was examined in CD1 mice, respectively. The results showed that, reduced Kidin220 expression was associated with tumorigenesis, metastasis, and overall survival of pancreatic cancer. Knockdown of Kidins220 promoted proliferation, colony formation and tumorigenic capacity of pancreatic cancer cells in vitro and in vivo, respectively. Kidins220 regulated pancreatic cancer cell migration through the EGFR/AKT/ERK signalling pathway. Furthermore, enhanced EMT was observed in the pancreatic cancer cell lines with the knockdown of Kidins220, underlying EGFR regulation. Kidins220 also affected cell invasion via MMP1. A reduced expression of Kidins220 was observed in pancreatic cancer, which is associated with disease progression, distant metastasis and poor prognosis. The loss of Kidins220 in pancreatic cancer may contribute to disease progression through the upregulation of EGFR and downstream signalling.

Background: ARHGAP11A, belongs to RhoGAPs family, is vital for cell motility. However, the role of ARHGAP11A in gastric cancer is obscure.Methods: The expression level of ARHGAP11A was analyzed by Oncomine database. The correlation of ARHGAP11A expression with immune infiltrates and associated gene markers was clarified by Tumor IMmune Estimation Resource and Gene Expression Profiling Interactive Analysis database. The correlation between ARHGAP11A expression and the patient prognosis was identified by Kaplan-Meier plotter and PrognoScan. Genetic changes of ARHGAP11A were analyzed by cBioPortal. The protein-protein interaction network and gene functional enrichment analysis were constructed and performed by GeneMANIA and Metascape.Results: We found that the expression levels of ARHGAP11A were elevated in various cancers including gastric cancer when compared with normal tissues. High expression of ARHGAP11A was significantly correlated with a better prognosis in gastric cancer. We revealed that the expression of ARHGAP11A was negatively associated with infiltration levels of CD8+ T cells, CD4+ T cells, macrophages and dendritic cells. In addition, ARHGAP11A expression was significantly correlated with gene markers of these immune cells. Lastly, gene functional enrichment analysis indicated that ARHGAP11A involved in regulating lymphocyte activation, cell division, cell killing, myeloid leukocyte differentiation and leukocyte apoptosis.Conclusion: Our findings demonstrated that ARHGAP11A was a valuable prognostic biomarker in gastric cancer. Further work is needed to validate its role and underlying mechanisms in regulating immune infiltrates.

The present study aimed to assess the role of tributyrin (TB) in regulating the growth and health status of juvenile blunt snout bream (Megalobrama amblycephala) through an 8-week feeding experiment. Six groups were fed experimental diets with added TB percentages of 0% (control group), 0.03%, 0.06%, 0.09%, 0.12% and 0.15%. The present results showed that TB supplementation in feed had some positive impacts on FW, WG, FCR and SGR, and the best results were found in the 0.06% TB group (P). However, TB supplementation in feed had no significant effects on SR, CF, VSI or whole-body composition (P>0.05). TB supplementation in feed increased antioxidant capacity and immunological capacity and attenuated the inflammatory response by increasing the activity of T-SOD, GPx, CAT and the levels of anti-inflammatory cytokines (IL-10 and TGF-β) and decreasing the levels of MDA and anti-inflammatory cytokines (TNF-α) (P). Furthermore, TB supplementation improved immunity by increasing the levels of immunoglobulins (IgM and IgG), C3 and IFN-γ (P). Surprisingly, 0.06%-0.12% TB supplementation significantly increased the content of IL-1β (P). However, TB supplementation in feed had no significant effects on the plasma content of GSH, HSP70, IL-8 and the activity of T-AOC (P>0.05). The possible mechanism was that TB activated PI3K/Akt/Nrf2 and inhibits the NF-κB signaling pathway, further regulating the mRNA levels of key genes with antioxidant capacity and the inflammatory response; for example, it increased the mRNA levels of Nrf2, Cu/Zn-SOD, HO-1, CAT, Akt, PI3K, GPx, IL-10, and TGF-β and decreased the mRNA levels of NF-κB and TNF-α (P). In addition, 0.06%-0.15% TB supplementation significantly increased the mRNA levels of IL-1β (P). TB supplementation in feed had no significant effects on the mRNA levels of HSP70, Mn-SOD and IL-8 (P>0.05). Evidence was presented that TB supplementation decreased the mortality rate caused by Aeromonas hydrophila challenge. In pathological examination, TB supplementation prevented hepatic and intestinal damage. Generally, TB supplementation improved the growth performance of juvenile blunt snout bream. Furthermore, TB supplementation activated PI3K/Akt/Nrf2 and inhibited the NF-κB signaling pathway, regulating health status and preventing hepatic and intestinal damage.

Background Gastric cancer is one of the most common and deadly malignancies worldwide. Despite recent medical progress, the 5-year survival rate of gastric cancer is still unsatisfactory. 5-fluorouracil (5-Fu) is one of the first-line antineoplastic treatments for gastric cancer, as it can effectively induce cancer cell apoptosis. However, the effect of 5-Fu is limited due to drug resistance of the malignant tumor. Previous studies have reported that Sotetsuflavone from Cycas revoluta Thunb. can markedly suppress lung cancer cell proliferation by apoptosis, though its effect on gastric cancer remains unknown. Aim To investigate the inhibitory effect of Cycas revoluta Thunb. and to determine whether it can overcome gastric cancer cell drug resistance to 5-Fu. Methods Cell viability was examined to determine whether the natural extract of Cycas revoluta Thunb. induced gastric cancer cell death. The half-maximal effective concentration and the half-maximal lethal concentration were calculatede. Wound-healing and transwell assays were performed to examine gastric cancer cell motility. Clonogenic assays were performed to investigate the synergistic effects of Cycas revoluta Thunb. with 5-Fu, and apoptotic bodies were detected by Hoechst staining. Western blotting was performed to examine the expression of related proteins and to investigate the molecular mechanism of Cycas revoluta Thunb.-induced cancer cell apoptosis. The expressions of proteins, including mammalian target of rapamycin (mTOR) and p-AKT, were detected in different combinations of treatments for 48 h, then analyzed by ECL detection. Results Gastric cancer cells were more sensitive to the natural extract of Cycas revoluta Thunb. compared to normal gastric epithelial cells, and the extract effectively inhibited gastric cancer cell migration and invasion. The extract improved the anti-cancer effect of 5-Fu by enhancing the chemosensitization of gastric cancer cells. Extract plus 5-Fu further reduced the expression of the drug-resistance-related proteins p-AKT and mTOR after 48 h compared to 5-Fu alone. Compared to 5-Fu treatment alone, mTOR and p-AKT expression was significantly reduced by about 50% and 75%, respectively. We also found that the natural extract of Cycas revoluta Thunb. further increased 5-Fu-induced gastric cancer cell apoptosis. Expression of apoptosis-related protein X-linked inhibitor of apoptosis protein and apoptosis inducing factor were significantly reduced and increased, respectively, in the 5-Fu-resistant gastric cancer line SGC-7901/R treated with extract plus 5-Fu, while the expression of survivin did not change. Conclusion The natural extract of Cycas revoluta Thunb. effectively inhibited gastric cancer cell growth and enhanced the anti-cancer effect of 5-Fu through the AKT-mTOR pathway.

To investigate the effect and mechanism of Xuefu Zhuyu Capsule (血府逐瘀胶囊, XZC) on pro-angiogenesis in the hindlimb ischemic model rats. A total of 100 Sprague Dawley rats were randomly divided into a model group, a regular-dose XZC group (0.48 g•kg-1•d-1) and a high-dose XZC group (0.96 g•kg-1•d-1) using random number table method. The model of hindlimb ischemic rats were made through femoral artery embolization with Bletilla microsphere agent. XZC were given on the first day after embolization surgery and lasted 5 days. Finally 72 models were obtained with 12 in each group for each time point. The lower ischemic limb was amputated on the third day after embolization surgery. Histopathological characters and the number of blood vessels of granulation tissues were observed at 36 and 48 h after amputation, respectively. The main genes were obtained from microarray analysis and were validated using real-time quantitative polymerase chain reaction. The vascular number of granulation tissues at both 36 and 48 h were characterized by new and fresh vessels. The number of angiogenesis in the high-dose XZC group at 36 and 48 h was greater compared with that in the regular-dose XZC and model groups (P

The present study evaluated the mechanisms governing insulin signaling, glucose metabolism, and lipogenesis in juvenile fish fed with different dietary leucine levels. Fish were fed six practical diets with graded leucine levels ranging from 0.90 to 2.94% of dry basis for 8 weeks. The trial results showed that, compared to the control group (0.90%), optimal dietary leucine level (1.72%) resulted in the up-regulation of mRNA expression related to insulin signaling pathway, including target of rapamycin (TOR), insulin receptor substrate 1 (IRS-1), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt). However, an excessive leucine level (2.94%) led to protein S6 kinase 1 (S6K1) overexpression and inhibited TOR, IRS-1, PI3K, and Akt mRNA expressions. The protein level of TOR, S6K1, IRS-1, PI3K, and Akt showed a similar result with mRNA level of these genes. Optimal dietary leucine level (1.72%) significantly improved plasma insulin content, while high level of leucine showed an inhibiting phenomenon. Optimal dietary leucine level (1.72%) could reduce plasma glucose by enhancing the ability of glycometabolism including improving glucose transporter 2 (GLUT2), glucokinase (GK) expressions and down-regulating phosphoenolpyruvate carboxykinase (PEPCK) expression. While an excessive leucine level (2.94%) resulted in high plasma glucose by inhibiting the ability of glycometabolism including lowering GLUT2 and GK expressions, and improving glucose-6-phosphatase (G6Pase) and PEPCK expressions. The relative expressions of pyruvate kinase (PK) and glycogen synthase (GS) were not significantly affected by dietary leucine levels. Dietary leucine level of 1.33% could improve plasma triglyceride content (TG) by enhancing lipogenesis including improving sterol-response element-binding protein 1 (SREBP1), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC), and glucose-6-phosphate dehydrogenase (G6PDH) expressions compared to the control group (0.90%). Total cholesterol (TC) was not significantly affected by dietary leucine levels. The present results indicate that optimal leucine level could improve glycolysis and fatty acid synthesis through improving insulin sensitivity in juvenile blunt snout bream. However, excessive dietary leucine level resulted in high plasma glucose, which led to insulin resistance by inhibiting the gene expressions of insulin signaling pathway and activating gluconeogenesis-related gene expression.

Objective To explore the intraperitoneal free cancer cell (IFCC) detection value of negative enrichment and immune fluorescence in situ hybridization (NEimFISH) on chromosomes (CEN) 8/17. Methods To verify the reliability of NEimFISH, 29 gastric cancer tumors, their adjacent tissues and greater omental tissues were tested. Our study then included 105 gastric cancer patients for IFCC. We defined patients as IFCC-positive if a signal was detected, regardless of the detailed cancer cell numbers. A comparison of clinicopathological features was conducted among IFCC groups. We also compared the diagnosis value and peritoneal recurrence predictive value among different detection methods. The comparison of IFCC number was also conducted among different groups. Results A cutoff of 2.5 positive cells could distinguish all benign tissue samples and 97% of malignant tissue samples in our study. Compared to intestinal gastric cancer, patients with diffuse gastric cancer tended to have more IFCCs (6 vs. 4, P=0.002). The IFCC counts were often higher in the lymphovascular invasion positive group than negative group (3 vs. 1, P=0.022). All IFCC samples that were considered positive using conventional cytology were also found to be positive using NEimFISH. When compared to conventional cytology and paraffin pathology, NEimFISH had a higher IFCC positive rate (68.9%) and higher one-year peritoneal recurrence predictive value with area under the curve (AUC) of 0.922. Conclusions Gastric cancer could be effectively diagnosed by NEimFISH. The IFCC number found using NEimFISH on CEN8/17 is closely associated with Lauren type and vascular invasion of cancer. NEimFISH is a reliable detection modality with a higher positive detection rate, higher one-year peritoneal recurrence predictive value and quantitative features for IFCC of gastric cancer.

Puerarin is an isoflavonoid isolated from the root of Pueraria lobata (Gegen in Chinese) that has been widely used to treat cardiovascular and cerebrovascular diseases in China. Here, we investigated the hypotensive effects and mechanisms of puerarin in spontaneously hypertensive rats. The qPCR array technique was used to determine the expression of hypertension-related genes. Then, the differentially expressed genes were analyzed using the STRING database. The systolic blood pressure and diastolic blood pressure of rats decreased after the administration of puerarin for nine weeks. Puerarin, but not losartan, also slowed the heart rate of rats. NO and cGMP levels were improved by puerarin. Eighteen differentially expressed hypertension-related genes were identified by comparing the model group with the control group and the high-dose puerarin group with the model group. NO and cGMP levels were increased by high-dose puerarin. High-dose puerarin increased the levels of the phosphorylated eNOS protein and decreased AT1 and Cav1 levels. Based on our results, eNOS was a key target in the mechanism by which puerarin reduced blood pressure, and puerarin represents a potential antihypertensive agent.

Biological complexity and the need for personalized medicine means that biomarker development has become increasingly challenging. Thus, new paradigms for research need to be created that bring together a different classifier of individuals. One potential solution is collaboration between biomarker development and Chinese medicine pattern classification. In this article, two examples of rheumatoid arthritis are discussed, including a new biomarker candidate casein kinase 2 interacting protein 1 (CKIP-1) and a micro RNA 214. The authors obtained a "snapshot" of pattern classification with disease in biomarker identification. Bioinformatics analyses revealed underlying biological functions of two biomarker candidates, in varying degrees, are correlated with Chinese medicine pattern of rheumatoid arthritis. The authors' initial attempt can provide a new window for studying the win-win potential correlation between the biomarkers and pattern classification in Chinese medicine.

BACKGROUND Low diagnostic efficiency and high metastasis and recurrence of nasopharyngeal carcinoma (NPC) result in bad survival. A novel diagnostic biomarker is of great importance for the improvement of NPC management. This study aimed to state the biological function and diagnostic values of miR-762 in NPC to provide a novel insight into the detection and therapy of NPC. METHODS The expression of miR-762 in NPC and healthy samples was detected by quantitative real-time polymerase chain reaction and its diagnostic value was evaluated by the receiver operating characteristic (ROC) analysis. The functional roles of miR-762 in the proliferation, migration, and invasion of NPC cells were assessed by CCK8 and Transwell assay. RESULTS The significant upregulation of miR-762 was observed in NPC serum compared with healthy controls, which was associated with the TNM stage and lymph node metastasis of NPC patients. The ROC curve showed that miR-762 could be a diagnostic biomarker for NPC with high accuracy and specificity. Additionally, miR-762 served as a tumor promoter, which could promote cell proliferation, migration, and invasion of NPC. CONCLUSION The upregulation of miR-762 in NPC is associated with the disease progression and diagnosis of NPC. miR-762 might be involved in the tumor progression of NPC, which provides a potential therapeutic target for the treatment and management of NPC.

An 8-week rearing trial was designed to appraise the dietary lysine levels on intestinal antioxidant capacity and immunity of grass carp fry. Six practical diets were prepared with graded levels of lysine (1.44, 1.79, 1.97, 2.44, 2.56 and 2.87% dry matter), and these diets were fed to grass carp fry. The results showed that the activities of intestinal antioxidant factors including catalase and glutathione peroxidase were markedly improved by the 2.44% dietary lysine compared with the control diet (1.44% dietary lysine) (P < 0.05). In terms of antioxidants, compared with the control diet, the 2.44% diet markedly upregulated the mRNA expression levels of target of rapamycin, S6 kinase1 and nuclear factor erythroid 2-related factor 2 pathway-related antioxidant genes, containing catalase and glutathione peroxidase 1α (P < 0.05) and downregulated the mRNA levels of Kelch-like ECH-associated protein 1 (P > 0.05). The mRNA levels of 4E-binding protein 2 showed the opposite trend compared with those of target of rapamycin, and the minimum value was observed in the group of 1.97% dietary lysine (P < 0.05). In terms of immunity, compared with the 1.44% diet, the 2.44% diet markedly suppressed the intestinal p38 mitogen-activated protein kinase and interferon γ2 mRNA levels (P < 0.05). Moreover, nuclear factor-kappa B p65, tumor necrosis factor α, interleukin 6, interleukin 8, and interleukin 15 mRNA levels all exhibited the same trend as p38 mitogen-activated protein kinase and interferon γ2; however, the difference among all the lysine treatments groups was not significant (P > 0.05). The anti-inflammatory cytokines transforming growth factor β2 and interleukin 4/13B mRNA levels in the intestine were remarkably upregulated by high dietary lysine levels (2.56 and 2.87%) (P < 0.05), and when the dietary lysine level reached 2.44%, the interleukin 4/13A mRNA levels were strikingly increased (P < 0.05). Overall, the data suggested that 2.44% dietary lysine could strengthen the immune and antioxidant capacities of grass carp fry via activating the target of rapamycin (TOR) signaling pathway, and suppressing the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway, which then improve the survival rate.

To investigate the combined anti-inflammatory effect of activating blood circulation and detoxifying Chinese medicines in unstable angina (UA) patients. This study was an open-labeled, randomized controlled trial conducted in 5 centers in Beijing. A total of 154 patients were randomized into two groups at a 1:1 ratio by random numbers. Based on the conventional treatment, patients in the activating blood circulation (ABC) group were treated with Guanxin Danshen Droping Pill (冠心丹参滴丸, 0.4 g, thrice daily), and patients in the activating blood circulation and detoxifying (ABCD) group were treated with Guanxin Danshen Droping Pill (0.4 g, thrice daily) and Andrographis tablet (0.2 g, thrice daily) for 4 weeks. The primary outcome was the serum level of high sensitive C reaction protein (hs-CRP), and the secondary outcome index included the serum levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), soluble CD40 ligand (sCD40L), thrombomodulin (TM), the score of angina pectoris, the score of blood stasis syndrome, and the score of Chinese medicine symptoms, observed at week 0 and week 4. A total of 144 patients completed the trial (ABC group, n=70; ABCD group, n=74). There were no significant differences in the clinical baseline characteristics between the two groups. When compared with the ABC group, ABCD group showed better performance in reducing the level of inflammatory factors, especially hs-CRP (P

Study Objectives. To study the relationship between perimenopausal insomnia (PI) and intestinal flora and the potential mechanism of Tianwang Buxin granules (TWBXG) in exerting its clinical efficacy. Methods. The subjects included 13 PI patients from the Hubei Provincial Hospital of TCM, Hubei University of TCM, and Wuhan Traditional Chinese Medicine Hospital, and the corresponding noninsomniac spouses of the patients were selected as controls. TWBXG was continuously administered for 4 weeks. The feces of PI patients and their noninsomniac spouses before and after treatment with TWBXG were collected. The intestinal flora composition of each group was detected by metagenomic sequencing, and the efficacy of TWBXG was evaluated by the PSQI scale. Results. Compared with the control group, the model group showed an increase in the abundance of Roseburia faecis, Ruminococcus, Prevotella copri, Fusicatenibacter saccharivorans, and Blautia obeum, while those of Bacteroides, fecal Bacteroidetes, and Faecalibacterium prausnitzii were decreased. Compared with pretreatment, the PSQI score was significantly reduced ( P < 0.05 ), the abundance of Bacteroides, fecal Bacteroidetes, and Faecalibacterium prausnitzii increased, and that of Roseburia faecis, Ruminococcus, Prevotella copri, Fusicatenibacter saccharivorans, and Blautia obeum decreased after treatment. However, there was still a certain gap in the abundance of related flora in the treatment group compared with the control. Conclusion. PI is associated with disturbances in the intestinal flora and is mainly related to the disorders of Roseburia faecis, Ruminococcus, Prevotella copri, Fusicatenibacter saccharivorans, Blautia obeum, Bacteroides, fecal Bacteroidetes, and Faecalibacterium prausnitzii. TWBXG can effectively treat PI, and its effect may be achieved by regulating the disordered intestinal flora. Clinical Trials. The study was registered in the Chinese clinical trial registry and approved by the World Health Organization clinical trial registration platform (Effects of the modified Tianwang Buxin granule and modified Tianwang Buxin decoction pieces on insomnia: a randomized, controlled trial, ChiCTR-IPR-17011549).