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Background: The prognostic value of human epididymis protein 4 (HE4) in patients with ischemic cardiomyopathy (ICM) is unknown.Methods: A total of 103 patients with ICM were prospectively enrolled in this study from Hunan Provincial People's Hospital between February 2019 and June 2019. All patients were tested for HE4 levels at baseline and follow-up. Endpoints of the study included cardiovascular death and heart failure-related hospitalization.Results: A total of 96 patients with ICM were included for analysis. After a mean follow-up period of 263 (153-313) days, cardiovascular events were observed in 45 patients. Serum HE4 levels in patients with events were significantly higher than those in patients without events [188.70 (113.35-326.82) pmol/L versus 92.90 (61.50-123.20) pmol/L, P < 0.001]. Multivariate Cox regression analysis revealed that HE4 [χ2: 9.602, hazard ratio (HR): 1.003, 95% confidence interval (CI): 1.001-1.005, P = 0.002] and age [χ2: 4.55, HR: 1.044, 95% CI: 1.003-1.085, P = 0.033] were independent predictors of events. After adjusting for age and sex, the risk of events in patients with HE4 > 100.2 pmol/L was higher than that in patients with HE4 ≤ 100.2 pmol/L [HR: 3.372, 95% CI: 1.409-8.065, P < 0.001].Conclusion: HE4 is an independent predictor of cardiovascular death and heart failure-related rehospitalization in patients with ICM. [ABSTRACT FROM AUTHOR]

Background: Mannose-binding lectin (MBL) is an important protein in the lectin pathway of the immune system. This study explores the association between MBL polymorphism and the susceptibility to tuberculosis (TB). The association between the MBL2 polymorphisms and serum MBL levels is also analyzed in the present study.Methods: A total of 112 inpatients with pulmonary TB and 120 healthy controls were recruited to participate in this case-control study. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR-RFLP) technology was used to genotype MBL gene (variants in -221Y/X and exon l codons 54 A/B). Serum MBL level was assayed by human MBL ELISA kit. Demographic data and exposure information were also obtained from the study participants.Results: Genotypes YA/YA of MBL gene were more prevalent in the healthy control group than in the TB patient (P =0.038, OR, 0.57; 95% CI, 0.34-0.97) and genotypes XA/XA were less frequent in the healthy control group (P =0.007, OR, 6.42; 95% CI, 1.39-29.67). The resistant diplotype was more frequently found in the younger patients and retreatment cases with TB in MBL gene sites -221Y/X or codon 54 A/B. X/Y and A/B polymorphisms were strong determinants of serum MBL levels.Conclusion: The polymorphisms of MBL gene may be associated with susceptibility to TB and the recurrence of TB. The YA/YA may be a protected diplotype against TB. [ABSTRACT FROM AUTHOR]

Background: Nutrition support is a common means for patients with gastric cancer, especially for those undergoing elective surgery. Recently, enteral immunonutrition (EIN) was increasingly found to be more effective than enteral nutrition (EN) in enhancing the host immunity and eventually improving the prognosis of gastric cancer patients undergoing gastrectomy. However, the results reported were not consistent. This meta-analysis aimed to assess the impact of EIN for patients with GC on biochemical, immune indices and clinical outcomes.Methods: Four electronical databases (Medline, EMBASE, Scopus and Cochrane library) were used to search articles in peer-reviewed, English-language journals. Mean difference (MD), Relative risk (RR), or standard mean difference (SMD) with 95% confidence interval (CI) were calculated. Heterogeneity was assessed by Cochrane Q and I2 statistic combined with corresponding P-value. The analysis was carried out with RevMan 5.3.Results: Seven studies involving 583 patients were eligible for the pooled analysis. EIN, when beyond a 7-day time-frame post-operatively (D ≥ 7), increased level of CD4+ (SMD = 0.99; 95% CI, 0.65-1.33; P < 0.00001), CD4+/ CD8+ (SMD = 0.34; 95% CI, 0.02-0.67; P = 0.04), the IgM (SMD = 1.15; 95% CI, 0.11-2.20; P = 0.03), the IgG (SMD = 0.98; 95% CI, 0.55-1.42; P < 0.0001), the lymphocyte (SMD = 0.69; 95% CI, 0.32-1.06; P = 0.0003), and the proalbumin (SMD = 0.73; 95% CI, 0.33-1.14; P = 0.0004). However, those increased effects were not obvious within a 7-day time-frame post-operatively (D < 7). The levels of CD8+ and other serum proteins except proalbumin were not improved both on D ≥ 7 and D < 7. Clinical outcomes such as systemic inflammatory response syndrone (SIRS) (MD, - 0.89 days; 95% CI, - 1.40 to - 0.39; P = 0.005), and postoperative complications (RR, 0.29; 95% CI, 0.14-0.60; P = 0.001) were significantly reduced in EIN group. Pulmonary infection and length of hospitalization (LHS) were not improved no matter what time after surgery.Conclusions: EIN was found to improve the cellular immunity, modulate inflammatory reaction and reduce postoperative complication for GC patients undergoing radical gastrointestinal surgery. Exclusion of grey literature and non-English language studies was the key limitation in this study. [ABSTRACT FROM AUTHOR]

Background: Recent studies have implicated that members of the DICKKOPF (DKK) were causally involved in large number of human cancers. This study was designed to investigate the relationship between the genetic variations of DKK family genes and the risk of gastric cancer (GC).Methods: Six SNPs (single nucleotide polymorphisms) of DKK family genes, including rs2241529 in DKK1, rs3733635, rs17037102 and rs419764 in DKK2, rs3206824 in DKK3 and rs2073664 in DKK4, were selected and genotyped by restriction fragment length polymorphism (RFLP) and TaqMan SNP genotyping methods in 409 GC cases and 554 cancer-free controls in the Han population in eastern China.Results: None of the six SNPs achieved significant association with the overall GC risk and stratified analysis by age, gender, smoking status, drinking status, tumor location and pathological classification confirmed these non-significant associations.Conclusions: Our study indicated that the studied six SNPs of DKKs would not be the risk factors for GC in this Han Chinese population. Studies of larger population for different ethnicities will be needed to warrant our findings. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence supports the pivotal roles of adipocytes in breast cancer progression. Tumour induced beige/brown adipose tissue differentiation contributes to the hypermetabolic state of the breast cancer. However, the mediators and mechanisms remain unclear. Methods: Survival probabilities were estimated using the Kaplan–Meier method based on immunohistochemistry results. Biochemical studies were performed to characterize the novel interrelation between breast cancer cells and adipocytes. Results: We show that tumour-surrounding adipocytes exhibit an altered phenotype in terms of upregulated beige/brown characteristics and increased catabolism associated with an activated state characterized by the release of metabolites, including free fatty acids, pyruvate, lactate and ketone bodies. Likewise, tumour cells cocultivated with mature adipocytes exhibit metabolic adaptation and an aggressive phenotype in vitro and in vivo. Mechanistically, we show that tumour cells induce beige/brown differentiation and remodel metabolism in resident adipocytes by exosomes from the co-culture system that carry high levels of miRNA-144 and miRNA-126. miRNA-144 promotes beige/brown adipocyte characteristics by downregulating the MAP3K8/ERK1/2/PPARγ axis, and exosomal miRNA-126 remodels metabolism by disrupting IRS/Glut-4 signalling, activating the AMPK/autophagy pathway and stabilizing HIF1α expression in imminent adipocytes. In vivo inhibition of miRNA-144 or miRNA-126 decreases adipocyte–induced tumour growth. Conclusions: These results demonstrate that by inducing beige/brown differentiation and enhancing catabolism in recipient adipocytes, exosomal miRNA-144 and miRNA-126 from the tumour-adipocyte interaction reprogram systemic energy metabolism to facilitate tumour progression. [ABSTRACT FROM AUTHOR]

Emerging evidence supports the pivotal roles of cancer-associated cachexia in breast cancer progression. However, the mediators and mechanisms that mediate cancer-induced cachexia remain unclear. Here, we show that breast cancer-derived exosomes alter adipocytes and muscle cells in terms of increased catabolism characterized by the release of metabolites. Likewise, tumour cells cocultivated with mature adipocytes or C2C12 exhibit an aggressive phenotype through inducing epithelial-mesenchymal transition. Mechanistically, we show that cancer cell-secreted miR-155 promotes beige/brown differentiation and remodel metabolism in resident adipocytes by downregulating the PPARγ expression, but does not significantly affect biological conversion in C2C12. In vitro the use of propranolol ameliorates tumour exosomes-associated cachectic wasting through upregulating the PPARγ expression. These results demonstrate that cancer-derived exosomes reprogram systemic energy metabolism and accelerate cancer-associated cachexia to facilitate tumour progression. [ABSTRACT FROM AUTHOR]

Background: Associations between adipokines and bone mineral density (BMD) in knee osteoarthritis (OA) remain indistinct. The aim of this study was to investigate the cross-sectional associations between serum levels of adipokines and BMD in patients with knee OA.Methods: This study included 164 patients with symptomatic knee OA from the Anhui Osteoarthritis study. Serum levels of leptin, adiponectin, and resistin were measured using an enzyme-linked immunosorbent assay (ELISA). BMD at total body, spine, hip, and femur were measured by dual-energy X-ray absorptiometry (DXA).Results: In multivariable analyses, serum levels of leptin were significantly associated with reduced BMD at total body, hip, total femur, femoral neck, and femoral shaft (β = - 0.019, 95% CI -0.034 to - 0.005; β = - 0.018, 95% CI -0.034 to - 0.003; β = - 0.018, 95% CI -0.034 to - 0.002; β = - 0.016, 95% CI -0.032 to 0.000; β = - 0.026, 95% CI -0.046 to - 0.006; respectively). Serum levels of adiponectin were significantly and negatively associated with BMD at total femur and femoral shaft (β = - 0.007, 95% CI -0.013 to 0.000; β = - 0.011, 95% CI -0.018 to - 0.003; respectively). However, no significant associations were found between serum levels of resistin and BMD at any site measured.Conclusions: Serum levels of leptin and adiponectin were significantly and negatively associated with BMD, suggesting potentially detrimental effects of leptin and adiponectin on BMD in knee OA patients. [ABSTRACT FROM AUTHOR]

Background: Coronary heart disease (CHD) is a major cause of morbidity and mortality, and cardiac rehabilitation (CR) is still not well developed in mainland China. The objective of this study is to investigate the barriers associated with those seeking cardiac rehabilitation (CR) and to explore appropriate secondary prevention modalities tailored to the needs of Chinese patients with coronary heart disease (CHD).Methods: A consecutive series of eligible patients was recruited from the cardiac department of a teaching hospital in Nanjing, located in southeast China. Structured face-to-face interviews were conducted with 328 patients prior to hospital discharge. Patient preferences for seeking an outpatient CR program or an alternative outpatient self-choice, minimal-cost educational program were evaluated. Socio-demographic characteristics and clinical data were assessed. Additionally, patients were asked to provide the reasons affecting their choice.Results: Overall, only 14.3% patients preferred the standard CR program. Factors associated with non-participating were female gender (odds ratios [ORs], 6.05, 95% CI, 1.30-28.19), older age (ORs, 1.11, 95% CI, 1.04-1.19, per year), less education (ORs, 8.13, 95% CI, 2.83-23.38), low income (ORs, 3.26, 95% CI, 1.24-8.54), and having either basic medical care or a lack of health insurance (ORs, 10.01, 95% CI, 3.90-25.68). The most common reason for refusing to participate in CR was that patients could not afford it. Of the remaining patients, 65.8% patients chose self-choice educational programs, especially for female (ORs, 5.84, 95% CI, 2.67-12.79), older (ORs, 1.06, 95% CI, 1.02-1.11, per year), and low income (ORs, 2.14, 95% CI, 1.12-4.10) patients. The main reasons for their preferences were their desires for more information about disease and risk factors, the low cost, feasibility, and saving time.Conclusions: Multiple barriers, which may occur at the patient, health system, and societal levels, have prevented eligible patients from participating in CR programs. Self-choice educational programs, an alternative model incorporating more information, would strongly meet the needs of most patients. A feasible delivery format for secondary prevention should be provided for all CHD patients. [ABSTRACT FROM AUTHOR]

Background: Mannose-binding lectin (MBL) is an important protein in the lectin pathway of the immune system. This study explores the association between MBL polymorphism and the susceptibility to tuberculosis (TB). The association between the MBL2 polymorphisms and serum MBL levels is also analyzed in the present study., Methods: A total of 112 inpatients with pulmonary TB and 120 healthy controls were recruited to participate in this case-control study. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR-RFLP) technology was used to genotype MBL gene (variants in -221Y/X and exon l codons 54 A/B). Serum MBL level was assayed by human MBL ELISA kit. Demographic data and exposure information were also obtained from the study participants., Results: Genotypes YA/YA of MBL gene were more prevalent in the healthy control group than in the TB patient (P =0.038, OR, 0.57; 95% CI, 0.34-0.97) and genotypes XA/XA were less frequent in the healthy control group (P =0.007, OR, 6.42; 95% CI, 1.39-29.67). The resistant diplotype was more frequently found in the younger patients and retreatment cases with TB in MBL gene sites -221Y/X or codon 54 A/B. X/Y and A/B polymorphisms were strong determinants of serum MBL levels., Conclusion: The polymorphisms of MBL gene may be associated with susceptibility to TB and the recurrence of TB. The YA/YA may be a protected diplotype against TB.

Background: Recent studies have implicated that members of the DICKKOPF (DKK) were causally involved in large number of human cancers. This study was designed to investigate the relationship between the genetic variations of DKK family genes and the risk of gastric cancer (GC)., Methods: Six SNPs (single nucleotide polymorphisms) of DKK family genes, including rs2241529 in DKK1, rs3733635, rs17037102 and rs419764 in DKK2, rs3206824 in DKK3 and rs2073664 in DKK4, were selected and genotyped by restriction fragment length polymorphism (RFLP) and TaqMan SNP genotyping methods in 409 GC cases and 554 cancer-free controls in the Han population in eastern China., Results: None of the six SNPs achieved significant association with the overall GC risk and stratified analysis by age, gender, smoking status, drinking status, tumor location and pathological classification confirmed these non-significant associations., Conclusions: Our study indicated that the studied six SNPs of DKKs would not be the risk factors for GC in this Han Chinese population. Studies of larger population for different ethnicities will be needed to warrant our findings.

Objective: To evaluate the effect of dehydroepiandrosterone (DHEA) on infertility patients with diminished ovarian reserve undergoing in vitro fertilization., Methods: This is a prospective study. Ninety-five patients with diminished ovarian reserve were included in this study. Of them, 42 patients were randomly allocated to the DHEA group, who received DHEA 75 mg daily for three consecutive menstrual cycles prior to IVF cycles, and 53 patients were allocated to the control group, who entered IVF cycles directly. All patients were treated with the same ovarian stimulation protocol. Follicular fluid samples from both groups were collected for bone morphogenetic protein-15 (BMP-15) and growth differentiation factor-9 (GDF-9). Fluid from the first aspirated follicle without any visible blood contamination was carefully collected. In addition, day 3 Blood samples were collected pre- and post-treatment of DHEA for serum anti-Mullerian hormone (AMH), follicle stimulating hormone (FSH) and estradiol (E2) in the DHEA group., Results: The level of BMP-15 in follicular fluid samples from the DHEA group was significantly higher than that of the control samples (P=.000). Patients after DHEA treatment demonstrated a significantly higher level of AMH and a significantly lower level of FSH, E2 compared to themselves prior to DHEA therapy (P=.015; P=.036; P=.002; respectively). Moreover, the accumulated score of embryos was significantly higher in the DHEA group (P=.033)., Conclusions: These observations confirm the beneficial effect of DHEA for infertility patients with diminished ovarian reserve., Trial Registration: ChiCTR-TRC-14005002.

Background: Amino acid neurotransmitters and nitric oxide (NO) are involved in the pathogenesis of major depressive disorder (MDD). Here we want to establish whether changes in their plasma levels may serve as biomarker for the melancholic subtype of this disorder., Methods: Plasma levels of glutamic acid (Glu), aspartic acid (Asp), glycine (Gly), gamma-aminobutyric acid (GABA), and NO were determined in 27 medicine-naïve melancholic MDD patients and 30 matched controls. Seven of the MDD patients participated also in a follow-up study after 2 months' antidepressant treatment. The relationship between plasma and cerebral-spinal fluid (CSF) levels of these compounds was analyzed in an additional group of 10 non-depressed subjects., Results: The plasma levels of Asp, Gly and GABA were significantly lower whereas the NO levels were significantly higher in melancholic MDD patients, also after 2 months of fluoxetine treatment. In the additional 10 non-depressed subjects, no significant correlation was observed between plasma and CSF levels of these compounds., Conclusion: These data give the first indication that decreased plasma levels of Asp, Gly and GABA and increased NO levels may serve as a clinical trait-marker for melancholic MDD. The specificity and selectivity of this putative trait-marker has to be investigated in follow-up studies.

Background: Host cell autophagy is implicated in the control of intracellular pathogen. Escherichia coli (E.coli) is the most common organism caused single-germ enterobacterial peritonitis during peritoneal dialysis. In this study, we investigated autophagy of peritoneal mesothelial cells and its role in defense against E.coli., Results: Autophagy in human peritoneal mesothelial cell line (HMrSV5) was induced by lipopolysaccharide (LPS) in a dose-dependent and time-dependent way, which was demonstrated by increased expression of Beclin-1 and light chain 3 (LC3)-II, the accumulation of punctate green fluorescent protein-LC3, and a higher number of monodansylcadaverine-labeled autophagic vacuoles. After incubation of HMrSV5 cells with E.coli following LPS stimulation, both the intracellular bactericidal activity and the co-localization of E.coli (K12-strain) with autophagosomes were enhanced. Conversely, blockade of autophagy with 3-methyladenine, wortmannin or Beclin-1 small-interfering RNA (siRNA) led to a significant reduction in autophagy-associated protein expression, attenuation of intracellular bactericidal activity, and reduced co-localization of E.coli with monodansylcadaverine-labeled autophagosomes. In addition, treatment of HMrSV5 cells with LPS caused a dose-dependent and time-dependent increase in Toll-like receptor 4 (TLR4) expression. Both knockdown of TLR4 with siRNA and pharmacological inhibition of TLR4 with Polymyxin B significantly decreased LPS-induced autophagy. Furthermore, TLR4 siRNA attenuated remarkably LPS-induced intracellular bactericidal activity., Conclusions: Our findings demonstrated for the first time that LPS-induced autophagy in peritoneal mesothelial cells could enhance the intracellular bactericidal activity and the co-localization of E.coli with autophagosomes. The activation of TLR4 signaling was involved in this process. These results indicate that LPS-induced autophagy may be a cell-autonomous defense mechanism triggered in peritoneal mesothelial cells in response to E.coli infection.