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Objective We described our initial experience of a new integrated oncology phamaceutical care practice to enhance the quality of pharmacy service and patient care in Huashan hospital. Data sources: A retrospective study was performed from August 2019 to September 2020. Patients were described as integrated pharmacy service group and routine care group. Medication adherence of patients in integrated pharmacy service group was recorded by the online management system. Patient satisfaction and the cumulative incidence of emergency room (ER) and outpatient visit were evaluated between two groups. Data summary: In total, 323 patients received the integrating oncology pharmacy service. The percentage of the patients missing administration every day was reduced from 29.7% to 0.3% within a 40-day monitoring and intervention period. There was a significant difference on patient satisfaction with pharmacy service in two groups ( P < 0.05). Fewer patients in the integrated pharmacy service group visited clinic and ER compared with routine care group (33.1% vs. 59.2%; P < 0.05). Conclusions As a new practice model, the integrated program is adopted to provide patient care and ongoing monitoring for cancer patients. The practice model delivers high continuity of care for cancer patients and improves communication and collaboration between healthcare professionals and oncology patients. The practice also provides the potential of developing hospital pharmaceutical service and optimizing disease prevention and treatment strategies.

Background Changes in baseline resting heart rate (RHR) appear to predict new-onset hypertension (NOH). However, RHR is a dynamic anthropometric parameter; thus, the association between changes in RHR and NOH requires further investigation. Methods We studied 10 403 participants who were initially normotensive and who had at least one routine health examination at baseline and 1 year later during 2011-2016. We compared the RHR between the baseline and 1-year follow-up. We defined hypertension as SBP ≥140 mmHg or DBP ≥90 mmHg. Participants were divided into three groups: RHR decreased, RHR unchanged [from 0 to 10 beats per minute (bpm)], and RHR increased ≥10 bpm. Cox regression analysis was performed to calculate relative risk with 95% confidence intervals (CIs) for the association between NOH and RHR change. Results During a mean follow-up period of 2.42 years, 1173 (11.28%) participants developed hypertension. After adjusting for age, sex, SBP, DBP, RHR and other confounders obtained at baseline, and compared with participants with unchanged RHR, participants with decreased RHR had a 17% decreased risk of NOH (adjusted hazard ratio: 0.83, 95% CI 0.73-0.95), whereas subjects with RHR that increased ≥10 bpm had a 23% increased risk of NOH (adjusted hazard ratio: 1.23, 95% CI 1.04-1.46). Conclusion A 1-year increase in RHR for initially normotensive subjects is an independent risk factor for subsequent hypertension.

SummaryAccumulating evidence suggests that a disruption of early brain development, in which insulin-like growth factor-2 (IGF-2) has a crucial role, may underlie the pathophysiology of schizophrenia. Our previous study has shown that decreased serum IGF-2 was correlated with the severity of psychopathology in patients with schizophrenia. Here we conducted a prospective observation trial to investigate the effects of atypical antipsychotics on serum IGF-2 level and its relationship with clinical improvements in schizophrenia patients. Thirty-one schizophrenia patients with acute exacerbation and 30 healthy individuals were recruited in this study. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and serum IGF-2 levels were determined using ELISA. We found that schizophrenia patients with acute exacerbation had lower serum IGF-2 levels than control individuals at baseline (PPvs. 426.99±124.26 ng/mL; t =−5.044, Pr=−0.522, P=0.006). Collectively, our findings demonstrated changes of serum IGF-2 response to improvements of negative symptoms in schizophrenia patients treated with atypical antipsychotics, suggesting that serum IGF-2 might be a treatment biomarker for schizophrenia.

Background: Elevated blood pressure (BP) is a risk factor for cognitive impairment. Objective: We aim to explore the association between the duration of hypertension in early adulthood, with cognitive function in midlife. Furthermore, we investigate whether this asssociation is altered among participants with controlled BP. Methods: This prospective study included 2,718 adults aged 18–30 years without hypertension at baseline who participated in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Duration of hypertension was calculated based on repeat measurements of BP performed at 2, 5, 7, 10, 15, 20, and 25 years after baseline. Cognitive function was assessed at Year-25 using the Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and Stroop test. Results: After multivariable adjustment, a longer hypertension duration was associated with worse verbal memory (RAVLT, p trend = 0.002) but not with processing speed (DSST, p trend = 0.112) and executive function (Stroop test, p trend = 0.975). Among subgroups of participants with controlled (BP

Accumulating evidence has suggested a dysfunction of synaptic plasticity in the pathophysiology of depression. Hydrogen sulfide (H2S), an endogenous gasotransmitter that regulates synaptic plasticity, has been demonstrated to contribute to depressive-like behaviors in rodents. The current study investigated the relationship between plasma H2S levels and the depressive symptoms in patients with depression. Forty-seven depressed patients and 51 healthy individuals were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) was used to evaluate depressive symptoms for all subjects and the reversed-phase high-performance liquid chromatography (RP-HPLC) was used to measure plasmaH2S levels. We found that plasma H2S levels were significantly lower in patients with depression relative to healthy individuals (P < 0.001). Compared with healthy controls (1.02 ± 0.34 μmol/L), the plasma H2S level significantly decreased in patients with mild depression (0.84 ± 0.28 μmol/L), with moderate depression (0.62 ± 0.21μmol/L), and with severe depression (0.38 ± 0.18 μmol/L). Correlation analysis revealed that plasma H2S levels were significantly negatively correlated with the HAMD-17 scores in patients (r = −0.484, P = 0.001). Multivariate linear regression analysis showed that plasma H2S was an independent contributor to the HAMD-17 score in patients (B = −0.360, t = −2.550, P = 0.015). Collectively, these results suggest that decreased H2S is involved in the pathophysiology of depression, and plasma H2S might be a potential indicator for depression severity.

Background and Aims: Central 5-hydroxytryptamine (5-HT) defects are responsible for the occurrence of sudden unexpected death in epilepsy (SUDEP). The DBA/1 mouse is an animal model of SUDEP since the mouse exhibits audiogenic seizure-induced respiratory arrest (S-IRA). The synthesis of central 5-HT is closely related to the gut microbiota. Moreover, emerging studies suggest a possible role for the microbiota in mitigating seizure likelihood. Based on this, we aimed to explore the effect of a high-tryptophan diet (HTD) on SUDEP as well as the synthesis and metabolism of central 5-HT. Furthermore, we investigated the involvement of the gut microbiota in this process.Methods: All DBA/1 mice were subjected to acoustic stimulation to induce seizures. Only those mice that exhibited S-IRA were randomly assigned to the normal diet (ND) group (n = 39) or HTD group (n = 53). After 1 month of dietary intervention, (1) S-IRA rates were evaluated, (2) the concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the plasma and brain were determined by ultra-high-pressure liquid chromatography, and (3) the fecal flora biodiversity and species composition were analyzed by 16S rDNA microbiota profiling.Results: The S-IRA rate in DBA/1 mice was significantly reduced in the HTD group compared with that in the control group. HTD increased the levels of 5-HT and 5-HIAA in both the telencephalon and midbrain. HTD significantly elevated the species richness and diversity of the gut microbiota. Moreover, there was a significant difference in the gut microbiota composition between the two groups, and the intestinal flora was dominated by Proteobacteria and Actinobacteria after HTD.Conclusions: HTD is efficient in lowering S-IRA rates and elevating the central 5-HT level in DBA/1 mice. The gut microbiota was altered after HTD intervention. The significant increase in Proteobacteria and Actinobacteria may be related to the SUDEP-protective effect of HTD. Our findings shed light on a candidate choice of dietary prevention for SUDEP.

Background: Triglyceride-glucose (TyG) index and homeostasis model assessment-insulin resistance (HOMA-IR) are related to insulin resistance (IR). The aim of this study was to assess the association between triglyceride-glucose index / HOMA-IR within young adults and congestive heart failure (CHF), and to explore whether triglyceride-glucose index can replace HOMA-IR as a surrogate marker for insulin resistance in predicting the risk of CHF.Methods：A total of 4992 participants between the ages of 18 and 30 were enrolled from the Coronary Artery Risk Development in Young Adults (CARDIA) investigation (from 1985 to 1986 [year 0]). Cox proportional hazard regression analysis was conducted for assessing correlations between baseline TyG index / HOMA-IR and congestive heart failure events, together with Receiver Operating Characteristic (ROC) Curve employed for scrutinizing TyG index / HOMA-IR and he risk of CHF.Results: During the 31-year follow-up period, 64 (1.3%) out of the 4992 participants developed congestive heart failure. In multivariable Cox proportional hazards models, adjusted for confounding factors for CHF, increased risk of CHF was associated with per-unit increase in TyG index (hazard ratio [HR] 2.8; 95% confidence interval [CI], 1.7-4.7) and HOMA-IR (HR 1.2; 95%CI, 1.1-1.3). Kaplan-Meier curve analysis showed that participants in the TyG index and HOMA-IR index Q4 group had a higher risk of congestive heart failure than those in the Q1 group. The area under curve (AUC) for TyG index and HOMA-IR consisted of 0.67 (95% CI, 0.6-0.742) and 0.675 (95%CI, 0.604-0.746), respectively. There were no significant differences between TyG index and HOMA-IR for AUC (P = 0.986).Conclusions: TyG index and HOMA-IR are independent risk factors for CHF. The TyG index can replace HOMA-IR in young adulthood as a surrogate marker for IR to predict the risk of CHF.

The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) lowered the diagnostic criteria for hypertension. We aimed to explore whether clustering of multiple risk factors are associated with the risk of new-onset hypertension defined by the 2017 ACC/AHA Hypertension Guideline. Subjects who attended ≥2 annual health examinations without baseline hypertension and cardiovascular disease were included. Hypertension was defined according to the 2017 ACC/AHA Hypertension Guideline. Seven predefined risk factors, including age, resting heart rate, overweight or obesity, dyslipidemia, hyperuricemia, impaired glucose regulation, and a poor estimated glomerular filtration rate, were analyzed. A composite, individual-level, cumulative score incorporating these seven risk factors (no = 0 point; yes = 1 point; total range of 0–7 points) was calculated. The association between the cumulative score and the risk of hypertension was analyzed using a Cox regression model. A total of 4424 (21.6%) of 20,190 subjects included had new-onset hypertension during a follow-up duration of 3.6 years. Compared with subjects with 0 points, the adjusted hazard ratios (95% confidence intervals) for the development of hypertension for those with 1, 2, 3, and ≥4 points were 1.21 (1.07–1.38), 1.34 (1.19–1.52), 1.44 (1.26–1.63), and 1.64 (1.44–1.87), respectively (P

Hyperuricemia is reportedly associated with poor outcome in acute heart failure (AHF). The association between changes in Uric acid (UA) levels with renal function change, diuretic doses, and mortality in patients with AHF were studied.Consecutive patients hospitalized with AHF were reviewed (n = 535). UA levels were measured at admission and either at discharge or on approximately the seventh day of admission. Patients with an UA change in the top tertile were defined as having an increase (UA-increase) and were compared to those outside the top tertile (non-UA-increase). The endpoint was all-cause mortality, with a mean follow-up duration of 22.2 months. Patients in the UA-increase group presented with greater creatine increase (P 0.001), and were administered a higher average daily dose of loop diuretic (P = 0.016) compared with the non-UA-increase group. In-hospital UA-increase was associated with higher risk of mortality even after adjusting for confounding variables including creatine change and diuretic dosage [harzard ratio (HR) 1.53, 95% confidence interval (CI) 1.02-2.30, P = 0.042]. In patients with hyperuricemia on admission, UA-increase was associated with increased mortality (adjusted HR 2.21, 95% CI 1.38-3.52, P = 0.001). Whereas, in those without admission hyperuricemia, UA-increase had no significant association with mortality.An increase in UA during in-hospital treatment is associated with an increase in creatine levels and daily diuretic dose. Mortality associated with increased UA is restricted to patients who already have hyperuricemia at admission. A combination of UA levels at admission and UA changes on serial assessment during hospitalization may be additional value in the risk stratification of AHF patients.

Background 2-oxoglutarate (2OG), an intermediate metabolite in the tricarboxylic acid cycle, has been found to associate with chronic heart failure (HF), but its effect on short-term adverse outcomes in patients with acute HF (AHF) is uncertain. Methods This prospective cohort study included 411 consecutive hospitalized patients with AHF. During hospitalization, fasting plasma samples were collected within the first 24 h of admission. Plasma 2OG levels were measured by hydrophilic interaction liquid chromatography-liquid chromatography tandem mass spectrometry (HILIC-LC/MS/MS). All participants were followed up for six months. Multiple logistic regression was used to determine the odds ratio (OR) and 95% confidence interval (CI) for primary outcomes. Results The AHF cohort consisted of HF with preserved ejection fraction (EF) (64.7%), mid-range EF (16.1%), and reduced EF (19.2%), the mean age was 65 (±13) years, and 65.2% were male. Participants were divided into two groups based on median 2OG levels (μg/ml): low group (

Aims Recent studies have shown that the choline-derived metabolite trimethylamine N-oxide (TMAO) is a biomarker that promotes cardiovascular disease through the induction of inflammation and stress. Inflammatory responses and stress are involved in the progression of calcified aortic valve disease (CAVD). Here, we examined whether TMAO induces the osteogenic differentiation of aortic valve interstitial cells (AVICs) through endoplasmic reticulum (ER) and mitochondrial stress pathways in vitro and in vivo. Methods and results Plasma TMAO levels were higher in patients with CAVD (n = 69) than in humans without CAVD (n = 263), as examined by liquid chromatography-tandem mass spectrometry. Western blot and staining probes showed that TMAO- induced an osteogenic response in human AVICs. Moreover, TMAO promoted ER stress, mitochondrial stress and NF-κB activation in vitro. Notably, the TMAO- mediated effects were reversed by the use of ER stress, mitochondrial stress and NF-κB activation inhibitors and siRNA. Mice treated with supplemental choline in a high fat diet had markedly increased TMAO levels and aortic valve thicknesses, which were reduced by 3,3-dimethyl-1-butanol (DMB, an inhibitor of trimethylamine formation) treatment. Conclusions Choline-derived TMAO promotes osteogenic differentiation through ER and mitochondrial stress pathways in vitro and aortic valve lesions in vivo. Translational perspective Trimethylamine-N-oxide (TMAO), a gut microbiota-generated metabolite, is associated with cardiovascular diseases. Here, we show that patients with calcified aortic valve disease (CAVD) have elevated circulating TMAO levels. TMAO induces osteogenic responses in human aortic valve interstitial cells via endoplasmic reticulum-mitochondrial stress in vitro and aggravates aortic valve lesions in mice. This may provide clues to the pathogenesis of CAVD and attractive potential targets for the prevention, diagnosis and treatment of this disease.

Heart failure (HF) is not uncommon among patients with hematologic malignancies (HM) undergoing hematopoietic stem cell transplantation (HSCT) and is associated with an increased mortality. Among HSCT patients without signs or symptoms of HF, groups with elevated and normal N-terminal probrain natriuretic peptide (NT-proBNP) levels have been poorly characterized in previous literature. Herein, we reviewed consecutive admissions for HM undergoing HSCT ( n = 301 ). Based on NT-proBNP levels and clinical signs or symptoms of HF at follow-up (one month after HSCT), patients were grouped into ENPH (elevated N T ‐ proBNP > 125 pg / mL , presence of HF symptoms or signs), ENAH (elevated N T ‐ proBNP > 125 pg / mL , absence of HF symptoms or signs), and NN (normal N T ‐ proBNP < 125 pg / mL ). ENPH, ENAH, and NN were observed in 22.9%, 54.5%, and 22.6% of patients, respectively. ENPH patients had a significantly higher baseline NT-proBNP level, followed by the ENAH and NN groups, respectively ( P < 0.001 ). Frequencies of HLA partially matched related donors, stem cell source (bone marrow+peripheral blood), and utilization of graft-versus-host disease prophylaxis regimens (ciclosporin+methotrexate+antithymocyte globulin±mycophenolate mofetil) were also the highest in the ENPH group, followed by ENAH and NN groups, respectively (all P < 0.05 ). Uric acid and hemoglobin levels, transplant type, and cyclophosphamide-based conditioning regimens utilized were similar between the ENAH and ENPH groups. We found that ENPH and ENAH are commonly observed in HM hospitalized for HSCT. Serum NT-proBNP levels may allow for earlier identification of HSCT patients at high risk of developing cardiac dysfunction.

Cognitive impairments are a core feature of schizophrenia. Klotho is an anti-aging protein with demonstrated cognitive-enhancing effects on the brain. The purpose of this study was to investigate the differences in levels of plasma klotho between patients with schizophrenia and healthy controls, as well as the relationship between klotho level and cognitive function in patients. Forty patients with schizophrenia and 40 gender- and age-matched healthy individuals were recruited. Positive and Negative Syndrome Scale (PANSS) was used to assess the psychopathology of patients. A neuropsychological battery was performed to evaluate the cognitive function of participants. Plasma klotho was measured using enzyme-linked immunosorbent assay. We show that patients with schizophrenia performed worse in the neurocognitive tests than the healthy controls. The levels of plasma klotho were significantly higher in schizophrenia patients than in healthy controls (p < 0.001). In patients, plasma klotho levels were positively correlated with cognitive function with regard to attention (p = 0.010), working memory (p < 0.001), verbal memory (p = 0.044), executive function (p < 0.001), and composite cognitive score (p < 0.001). Stepwise linear regression analysis shows that executive function had the highest correlation with plasma klotho levels (β = 0.896, t = 8.290, p < 0.001). Collectively, these results indicate that anti-aging protein klotho may be implicated in the pathogenesis of schizophrenia, and increased klotho may act as a compensatory factor for the preservation of cognitive function in schizophrenia. Further studies are needed to investigate the dynamic changes of klotho and the mechanisms by which klotho modulates cognition in schizophrenia.

Several studies show that even a level of urine albumin/creatinine ratio (UACR) within the normal range (below 30 mg/g) increases the risk of cardiovascular diseases. We speculate that mildly increased UACR is related to left ventricular hypertrophy (LVH) in patients with type 2 diabetes mellitus (T2DM). In this retrospective study, 317 patients with diabetes with normal UACR, of whom 62 had LVH, were included. The associations between UACR and laboratory indicators, as well as LVH, were examined using multivariate linear regression and logistic regression, respectively. The diagnostic efficiency and the optimal cutoff point of UACR for LVH were evaluated using the area under the receiver operating characteristic curve (AUC) and Youden index. Our results showed that patients with LVH had significantly higher UACR than those without LVH (P<0.001). The prevalence of LVH presented an upward trend with the elevation of UACR. UACR was independently and positively associated with hemoglobin A1c (P<0.001). UACR can differentiate LVH (AUC = 0.682, 95% CI (0.602–0.760),P<0.001). The optimal cutoff point determined with the Youden index was UACR = 10.2 mg/g. When categorized by this cutoff point, the odds ratio (OR) for LVH in patients in the higher UACR group (10.2–30 mg/g) was 3.104 (95% CI: 1.557–6.188,P=0.001) compared with patients in the lower UACR group (P=0.028). Overall, UACR below 30 mg/g is associated with LVH in patients with T2DM. The optimal cutoff value of UACR for identifying LVH in diabetes is 10 mg/g.

BACKGROUND Cardiac rupture often occurs after acute myocardial infarction due to complex and unclear pathogenesis. This study investigated whether metformin increases the incidence of cardiac rupture after myocardial infarction through the AMPK-MTOR/PGC-1α signaling pathway. MATERIAL AND METHODS An acute myocardial infarction (MI) mouse model was established. A series of experiments involving RT-qPCR, Western blot, TUNEL staining, and Masson staining were performed in this study. RESULTS Myocardial infarction occurred, resulting in the cardiac rupture, and the expression level of PGC-1α increased in the cardiac myocardium. Meanwhile, the proportion of myocardial NT-PGC-1α/PGC-1α decreased. The expression level of myocardial PGC-1α in MI mice with cardiac rupture after MI was significantly higher than that in the mice without cardiac rupture, and the ratio of myocardial NT-PGC-1α/PGC-1α was low. In addition, increasing the dose of metformin significantly increased the incidence of cardiac rupture after myocardial infarction in MI mice. High-dose metformin caused cardiac rupture in MI mice. Moreover, high-dose metformin (Met 2.0 nM) reduces the proportion of NT-PGC-1α/PGC-1α in primary cardiomyocytes of SD mice (SD-NRVCs [Neonatal rat ventricular cardiomyocytes]), and its effect was inhibited by Compound C (AMPK inhibitor). Further, after 3 days of treatment with high-dose metformin in MI mice, myocardial fibrin synthesis decreased and fibrosis was significantly inhibited. Meanwhile, cardiomyocyte apoptosis increased significantly. With the increase in metformin concentration, the expression level of myocardial LC3b gradually increased in MI mice, suggesting that metformin enhances the autophagy of cardiomyocytes. CONCLUSIONS These results suggest that metformin increases cardiac rupture after myocardial infarction through the AMPK-MTOR/PGC-1α signaling pathway.

Aberrant N-methyl-d-aspartate receptor (NMDAR) function has been implicated in the pathophysiology of schizophrenia. Hydrogen sulfide (H2S) is an endogenous gasotransmitter that regulates NMDAR function. The current study investigated the relationship between plasma H2S levels and both psychopathological and cognitive symptoms in schizophrenia. Forty-one patients with schizophrenia and 40 healthy control subjects were recruited in present study. Schizophrenic symptomatology was assessed using the Positive and Negative Syndrome Scale (PANSS). Cognitive function was evaluated with a neuropsychological battery including seven neurocognitive tests. Plasma H2S levels were measured by reversed-phase high-performance liquid chromatography (RP-HPLC). Patients with schizophrenia performed worse in all of the cognitive tests than the healthy controls except for the visual memory. Plasma H2S levels were significantly lower in patients with schizophrenia relative to healthy control subjects (F = 3.821, p = 0.007). Correlation analysis revealed a significant negative correlation between the H2S levels and the PANSS general scores (r = − 0.413, p = 0.007). Additionally, a positive association was observed between plasma H2S levels and working memory (r = 0.416, p = 0.007), visual memory (r = 0.363, p = 0.020), or executive function (r = 0.344, p = 0.028) in patients. Partial correlation analysis showed that the correlations between the H2S levels and the PANSS general scores, working memory, visual memory, or executive function were still significant when controlling for age, gender, years of education, BMI, duration of illness, and age of onset. The significant relations observed in the current study between H2S and the general psychopathological as well as cognitive symptoms suggest that decreased H2S is involved in the psychopathology and cognitive deficits of schizophrenia, and it might be a promising peripheral biomarker of schizophrenia.

Background Brain metastases (BM) from non-small cell lung cancer (NSCLC) are the most frequent intracranial tumors. To identify patients who might benefit from intracranial surgery, we compared the six existing prognostic indexes(PIs) and built a nomogram to predict the survival for NSCLC with BM before they intended to receive total intracranial resection in China. Methods First, clinical data of NSCLC presenting with BM were retrospectively reviewed. All of the patients had received total intracranial resection and were randomly distributed to developing cohort and validation cohort by 2:1. Second, we stratified the cohort using a recursive partitioning analysis(RPA), a score index for radiosurgery (SIR), a basic score for BM (BS-BM), a Golden Grading System (GGS), a disease-specific graded prognostic assessment (DS-GPA) and by NSCLC-RADES. The predictive power of the six PIs was assessed using the Kaplan–Meier method and the log-rank test. Third, univariate and multivariate analysis were explored, and the nomogram predicting survival of BMs from NSCLC was constructed using R 3.2.3 software. The concordance index (C-index) was calculated to evaluate the discriminatory power of the nomogram in the developing cohort and validation cohort. Results BS-BM could better predict survival of patients before intracranial surgery compared with other PIs. In the final multivariate analysis, KPS at diagnosis of BM, metachronous or synchronous BM and the histology of lung cancer appeared to be the independent prognostic predictors for survival. The C-index in the developing cohort and validation cohort were 0.75 and 0.71 respectively, which was better than the C-index of the other six PIs. Conclusions The new nomogram is a promising tool in further choosing the candidates for intracranial surgery among NSCLC with BM and in helping physicians tailor suitable treatment options before operation in clinical practice.

Background Hemoconcentration has been proposed as surrogate for changes in volume status among patients hospitalized with acute heart failure (AHF) and is associated with a favorable outcome. However, there is a dearth of research assessing the clinical outcomes of hospitalized patients with hemoconcentration, hemodilution and unchanged volume status. Methods We enrolled 510 consecutive patients hospitalized for AHF from April 2011 to July 2015. Hematocrit (HCT) levels were measured at admission and either at discharge or on approximately the seventh day of admission. Patients were stratified by delta HCT tertitles into hemodilution (ΔHCT ≤ − 1.6%), no change (NC, −1.6% 1.5%) groups. The endpoint was all-cause death, with a median follow-up duration of 18.9 months. Results Hemoconcentration was associated with lower left ventricle ejection fraction, as compared with NC and hemodilution groups, while renal function at entry, New York Heart Association class IV, and in-hospital worsening renal function (WRF) were not significantly different across the three groups. After multivariable adjustment, hemoconcentration had a lower risk of mortality as compared with hemodilution [hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.24–0.63, P

microRNA223 (miR-223) plays an important role in the development of atherosclerosis and ischemic stroke. It is involved in regulation of multiple physiological and pathophysiological processes such as cholesterol metabolism, endothelial cell (EC) function, and thrombosis. Here we investigated the role of methylation regulation of MIR-223 promoter region in atherosclerotic cerebral infarction (ACI) patients.A total of 23 patients with ACI and 32 healthy individuals were recruited. We performed bisulfite sequencing PCR and real-time PCR to detect methylation levels of MIR-223 promoter region and miR-223, respectively, in genomic DNA isolated from peripheral blood leukocytes.Mean methylation levels of a total of nine CpGs of MIR-223 promoter were significantly lower in ACI patients than in healthy individuals (p 0.01), and were also significantly lower in individuals with carotid atherosclerosis than those without carotid atherosclerosis (p 0.05). Meanwhile, miR-223 expression in leukocytes was significantly higher in ACI patients than in healthy individuals (p 0.05). miR-223 level was negatively correlated with mean methylation levels of MIR-223 promoter (r = -0.4451, p 0.01). The methylation level of MIR-223 promoter revealed a positive correlation with the circulating total cholesterol level (r = 0.318, p = 0.019).Hypomethylation of MIR-223 promoter is associated with atherosclerotic cerebral infarction.

Calcific aortic valve disease is a chronic inflammatory condition, and the inflammatory responses of aortic valve interstitial cells (AVICs) play a critical role in the disease progression. Double-stranded RNA (dsRNA) released from damaged or stressed cells is proinflammatory and may contribute to the mechanism of chronic inflammation observed in diseased aortic valves. The objective of this study is to determine the effect of dsRNA on AVIC inflammatory responses and the underlying mechanism. AVICs from normal human aortic valves were stimulated with polyinosinic-polycytidylic acid [poly(I:C)], a mimic of dsRNA. Poly(I:C) increased the production of IL-6, IL-8, monocyte chemoattractant protein-1, and ICAM-1. Poly(I:C) also induced robust activation of ERK1/2 and NF-κB. Knockdown of Toll-like receptor 3 (TLR3) or Toll-IL-1 receptor domain-containing adapter-inducing IFN-β (TRIF) suppressed ERK1/2 and NF-κB p65 phosphorylation and reduced inflammatory mediator production induced by poly(I:C). Inhibition of NF-κB, not ERK1/2, reduced inflammatory mediator production in AVICs exposed to poly(I:C). Interestingly, inhibition of NF-κB by prevention of p50 migration failed to suppress inflammatory mediator production. NF-κB p65 intranuclear translocation induced by the TLR4 agonist was reduced by inhibition of p50 migration; however, poly(I:C)-induced p65 translocation was not, although the p65/p50 heterodimer is present in AVICs. Poly(I:C) upregulates the production of multiple inflammatory mediators through the TLR3-TRIF-NF-κB pathway in human AVICs. The NF-κB activated by dsRNA appears not to be the canonical p65/p50 heterodimers.

Background: Currently, the treatment of symptomatic brain metastases from lung adenocarcinoma has remained difficult. Bevacizumab combined with chemotherapy is one of the standard treatments of lung adenocarcinoma. This study was designed to investigate the efficacy and safety of bevacizumab combined with chemotherapy in symptomatic brain metastases from lung adenocarcinoma that are not suitable for local treatments, and to explore the predictive value of baseline serum vascular endothelial growth factor (VEGF) for the treatment. Methods: We retrospectively reviewed 14 consecutive patients, between Jan 2015 and Jul 2017, with brain metastases from lung adenocarcinoma who received bevacizumab and chemotherapy to determine efficacy and toxicity. Kaplan-Meier method was used to estimate survival curves, and univariate and multivariate analyses were performed by Cox proportional hazard model. The primary endpoints were objective response rate (ORR) and intracranial ORR (iORR). The secondary endpoints were progression-free survival (PFS), intracranial PFS (iPFS), overall survival (OS) and disease control rate (DCR). Results: The efficacy of 12 patient was evaluated. Overall ORR was 25% (3/12) and the iORR of brain lesions was 33.3% (4/12). DCR was 75% (9/12). The median OS was 18.3 months, the median PFS was 6.7 months, and the median iPFS was 12 months. After 2 cycles of bevacizumab, 10 patients showed improved symptoms of central nervous system (CNS), and the symptom control rate was 83.3% (10/12). Head MRI showed that edema in the brain was greatly reduced in 6 patients, resulting in the lessened usage of dexamethasone. iPFS was significantly shorter in high VEGF group (3.6 vs . 8.0 m, P=0.02), and multivariate analysis showed a significant correlation between iPFS and serum baseline VEGF level (P=0.023). The most commonly adverse events of bevacizumab included leukopenia [5 (35.7%)], fatigue [3 (21.4%)], thrombocytopenia [3 (21.4%)], anemia [2 (14.3%)], which were mostly degree I and II. Conclusions: This study showed bevacizumab combined with chemotherapy could effectively control intracranial lesions, relieve symptoms, and improve the quality of life and survival of patients with brain metastases from lung adenocarcinoma. Serum baseline VEGF may be a predictor of efficacy of bevacizumab plus chemotherapy in the treatment of brain metastases from lung adenocarcinoma.

Background: Genetic factors underlying predisposition to Symptomatic Intracranial Atherosclerotic Stenosis (sICAS) remain unknown, the purpose of the present study was to identify genetic variants that confer susceptibility to sICAS in a Chinese Han population. Methods: The study population comprised of 379 Chinese individuals, including 193 patients with sICAS and 186 unrelated healthy controls. A total of 96 polymorphisms selected by genome-wide association or candidate-gene association studies of atherosclerosis and atherosclerotic diseases were examined in the present study with the use of Illumina VeraCode technology. Statistical analyses were performed with PLINK and SPSS software, and each genotype was assessed according to dominant, recessive, and additive genetic models. Results: Comparisons between subjects with sICAS and controls revealed that rs3798220 of the lipoprotein(a) gene (LPA) and rs9818870 of the muscle RAS oncogene homolog gene (MRAS) were significantly (P0.0005). Conclusion: LPA rs3798220 might be susceptibility loci for sICAS in Chinese Han individuals. Keywords: Symptomatic Intracranial Atherosclerotic Stenosis; risk factors; candidate gene; SNP.

A known cause of seizure-induced respiratory arrest is the deficiency in serotonergic neurotransmission. Tryptophan hydroxylase-2 (TPH2) is the rate-limiting enzyme of central serotonin (5-hydroxytryptamine) synthesis which converts l-tryptophan to 5-hydroxytryptophan. A recent study revealed a reduction in TPH2 protein expression in the brainstems of DBA/1 mice that developed recurrent seizure-induced respiratory arrest, whereas the activity of this protein was unexplored. Thus this study aims to investigate the association between intrinsic 5-hydroxytryptamine synthesis in the brainstem and the susceptibility for sudden unexpected death in epilepsy in DBA/1 mice. The effect of LY393558, a potent 5-hydroxytryptamine reuptake inhibitor with 5-HT1B/1D receptor antagonist properties, on seizure-induced respiratory arrest evoked by acoustic stimulation was also examined in DBA/1 mice. ELISA results showed significantly decreased TPH2 activity in the brainstems of untreated DBA/1 mice than that of C57BL/6J mice. Moreover, the concentrations of 5-hydroxytryptamine, 5-hydroxytryptophan and 5-HIAA in the brainstems of DBA/1 mice with or without acoustic stimulation were significantly lower than that of C57BL/6J mice. Acute administration of LY393558 also significantly reduced seizure-induced respiratory arrest in DBA/1 mice. These observations provide novel evidences for the hypothesis that 5-hydroxytryptamine deficiency might be a potential cause of seizure-induced respiratory arrest.

Accumulating evidence has shown that insulin-like growth factors (IGFs) are implicated in schizophrenia. Altered serum levels of IGF-1 have been found in schizophrenia patients and are associated with psychopathological symptoms. However, whether there is a relationship between IGF-1 and cognitive impairment in schizophrenia remains unknown. Thirty schizophrenia patients and 26 healthy controls were recruited for this study. The Positive and Negative Syndrome Scale was adopted to assess schizophrenic symptoms, and a battery of neuropsychological tests was employed to evaluate cognitive function. Serum IGF-1 content was determined by enzyme-linked immunosorbent assay (ELISA). We found that patients with schizophrenia performed more poorly than healthy controls in most cognitive tasks, excluding visual memory. The serum IGF-1 concentrations in schizophrenia patients were much lower than those in controls. Correlation analyses revealed that the levels of serum IGF-1 were positively correlated with executive function and attention scores in patients. Furthermore, IGF-1 was an independent contributor to deficits in executive function and attention among schizophrenia patients. Collectively, serum IGF-1 levels were significantly correlated with cognitive performance in schizophrenia patients, indicating that decreased IGF-1 levels might contribute to the pathophysiology of schizophrenia-associated cognitive impairments. The regulation of IGF-1 signaling might be a potential treatment strategy for cognitive impairments in schizophrenia.

OBJECTIVES This study aimed to develop a cumulative score composed of seven risk factors: age, resting heart rate, overweight or obesity, dyslipidemia, hyperuricemia, impaired glucose regulation, and impaired estimated glomerular filtration rate (eGFR), to evaluate the risk of new-onset hypertension. METHODS We retrospectively conducted a cohort study in 23 665 participants free from hypertension at baseline, who attended at least two annual health examinations between 2011 and 2016. We defined hypertension as SBP of 140 mmHg or less and/or DBP of at least 90 mmHg, according to the 2010 Chinese guidelines for the management of hypertension. We computed a composite, individual-level cumulative score incorporating all seven risk factors (no = 0 point; yes = 1 point; total range 0-7 points). Cox regression was used to analyze the association between cumulative score and risk of hypertension. RESULTS A total of 2305 participants developed hypertension during a median follow-up period of 3.6 years. Compared with participants with 0 points, the adjusted hazard ratios (95% confidence intervals) for the development of hypertension for those with 2, 3, and at least 4 points were 1.61 (1.29-2.02), 2.05 (1.64-2.57) and 2.77 (2.22-3.46), respectively (P trend

Cognitive deficits represent a core feature of schizophrenia. Previous studies have demonstrated that plasma asymmetric dimethylarginine (ADMA) was increased in patients with schizophrenia and correlated with cognitive impairments. Atypical antipsychotics can produce cognitive benefits in schizophrenia patients. In this study, we conducted a prospective observation trial to explore whether plasma ADMA may serve as an indicator for evaluating cognitive improvements induced by atypical antipsychotics in patients with schizophrenia. A total of 41 schizophrenia patients with acute exacerbation were enrolled and 29 patients completed this study. These recruited patients were drug-naive or had no exposure to antipsychotics for at least 3 months. Thirty healthy individuals were recruited as a control group. Positive and Negative Syndrome Scale (PANSS) and a neuropsychological battery were used to evaluate schizophrenic symptoms and cognitive function, respectively. Plasma ADMA was measured by high-performance liquid chromatography (HPLC). We found that schizophrenia patients with acute exacerbation had significantly poorer cognitive performances and higher plasma ADMA levels than control individuals (p < 0.05). After 2 months of atypical antipsychotic treatment, patients showed significant improvements in processing speed, working memory, attention, and executive function (all p < 0.01). Plasma ADMA levels in patients after treatment were significantly decreased compared to baseline (2.42 ± 0.84 vs. 1.55 ± 0.34 μmol/L; t = 6.491, p < 0.001). Correlation analysis reveals that there is a significant correlation of the decrease in ADMA with improvements in working memory (r = −0.413, p = 0.026) and attention (r = −0.417, p = 0.025). Collectively, our results suggest that atypical antipsychotics improve cognitive function in schizophrenia patients with acute exacerbation, in parallel with decreased plasma ADMA levels. Plasma ADMA levels may be an indicator of cognitive recovery in schizophrenia.

To compare the pathological changes in cartilage derived from rats that developed osteoarthritis either by joint immobilization or by strenuous treadmill running in order to better understand their respective pathomechanism.A total of 24 male Wistar rats were randomly assigned to three groups: sedentary control (CON), immobilization (IM), and strenuous running (SR). For rats in the IM group, unilateral knee joint was immobilized in flexion. Rats in the SR group underwent treadmill running with high intensity. Eight weeks later, all animals were sacrificed. Femoral condyles were collected to take histological observation for cartilage characteristic and immunohistochemistry for collagen type II. In addition, cartilage samples were obtained to assess gene expression of aggrecan, collagen type II, biglycan, and fibromodulin by quantitative RT-PCR.Gross and histological observation showed osteoarthritic changes in groups SR and IM; however, more severe cartilage degradation was revealed in the latter. Proteoglycan and collagen II content decreased in groups SR and IM in comparison to group CON, with more loss in group IM. In group SR, mRNA levels in femoral cartilage were found to be unaltered for all the molecules measured. On the contrary, these molecules were significantly downregulated in group IM.Differences in gross observation, histological characteristics, and gene expression of proteoglycans and collagen II suggest that both knee immobilization and strenuous running would lead to degenerative change of cartilage, but at different stages of the degenerative process.

It is uncertain that the effect of free triiodothyronine (FT3) within normal ranges on initial severity and early functional outcomes in acute ischemic stroke (AIS) patients with Intracranial Atherosclerotic Stenosis (ICAS). The predictive values of white blood cell (WBC) and FT3 are also unclear in symptomatic ICAS (sICAS) patients.We consecutively reviewed 848 ischemic stroke patients admitted into Xiangya Hospital within 72 h after symptom onset. sICAS was defined as AIS patient with degree of ICAS ≥50% proved by magnetic resonance angiography, computed tomography angiography or digital subtraction angiography. WBC and FT3 were assessed within 24 h after admission. Neurological severity was evaluated on admission using the National Institutes of Health Stroke Scale (NIHSS). Stroke outcomes were defined by the modified Rankin Scale (mRS) on the 14th day after admission.Logistic regression analysis showed that hypertension, lower FT3 and higher WBC concentrations independently associated with severe stroke [FT3 (odds ratio(OR) = 0.543, 95% confidence interval(95% CI): 0.383-0.769); hypertension (OR = 0.436, 95% CI: 0.238-0.800); WBC (OR = 1.17; 95% CI:1.041-1.316]. Besides, lower FT3, higher FT4, higher WBC and higher plasma glucose concentrations independently associated with unfavorable outcomes [FT3 (OR = 0.460; 95% CI: 0.306-0.690); FT4 (OR = 1.151; 95% CI: 1.055-1.255); WBC (OR = 1.178; 95% CI: 1.039-1.334); Plasma glucose (OR = 1.160; 95% CI: 1.002-1.342)].Lower FT3 levels within normal ranges and higher WBC count are independently associated with the severity and early poor prognosis of sICAS simultaneously, FT3 and WBC count might be important biomarkers for sICAS patients.

Objective: Medullary breast carcinoma is a rare breast carcinoma with good prognosis. Although it has been established that axillary lymph node metastasis is a poor prognostic factor, little is known about the relationship between axillary lymph node metastasis and clinicopathological characteristics of medullary breast carcinoma patients. The aim of this study was to identify factors that predict occurrence of axillary lymph node metastasis in medullary breast carcinoma patients. Methods: We performed a retrospective study of axillary lymph node status and the relevant clinicopathological characteristics in 49 triple-negative medullary breast carcinoma patients with axillary lymph node dissection between November 2004 and July 2011. Results: A total of 49 patients were enrolled in the study. Fourteen patients (28.6%) had axillary lymph node metastasis that was confirmed pathologically. Axillary lymph node metastasis was not associated with age, menopausal status, primary tumor size or its location, the degree of inflammation within the tumor or mitotic count. However, we found a statistically significant association between axillary lymph node metastasis and Ki67 labeling index in primary tumors (P < 0.001). Conclusions: There is a positive association between Ki67 labeling index in the primary tumor and axillary lymph node metastasis in triple-negative medullary breast carcinoma patients.

Calcific aortic valve disease (CAVD) is characterized by chronic inflammation and progressive calcification in valve leaflets. Aortic valve interstitial cells (AVICs) play a critical role in the pathogenesis of CAVD. Previous studies show that stimulation of Toll-like receptor (TLR) 2 or TLR4 in AVICs in vitro up-regulates the expression of osteogenic mediators. Double-stranded RNA (dsRNA) can activate pro-inflammatory signaling through TLR3, the NLRP3 inflammasome and RIG-I-like receptors. The objective of this study is to determine the effect of dsRNA on AVIC osteogenic activities and the mechanism of its action. Methods and results: AVICs isolated from normal human valves were exposed to polyinosinic-polycytidylic acid [poly(I:C)], a mimic of dsRNA. Treatment with poly(I:C) increased the production of bone morphogenetic protein-2 (BMP-2), transforming growth factor beta-1 (TGF-β1) and alkaline phosphatase (ALP), and resulted in calcium deposit formation. Poly(I:C) induced the phosphorylation of NF-κB and ERK1/2. Knockdown of TLR3 essentially abrogated NF-κB and ERK1/2 phosphorylation, and markedly reduced the effect of poly(I:C) on the production of BMP-2, TGF-β1 and ALP. Further, inhibition of either NF-κB or ERK1/2 markedly reduced the levels of BMP-2, TGF-β1 and ALP in cells exposed to poly(I:C). Conclusion: Poly(I:C) up-regulates the production of BMP-2, TGF-β1 and ALP, and promotes calcium deposit formation in human AVICs. The pro-osteogenic effect of poly(I:C) is mediated primarily by TLR3 and the NF-κB and ERK1/2 pathways. These findings suggest that dsRNA, when present in aortic valve tissue, may promote CAVD progression through up-regulation of AVIC osteogenic activities.

Lung cancer is the leading cause of cancer death in men and women worldwide. Brain metastasis (BMs) of non-small cell lung cancer (NSCLC) is the most important cause of death. This study aimed to explore the association of epidermal growth factor receptor (EGFR) mutations and BMs in NSCLC. We analyzed 50 NSCLC patients with BMs and 50 match-paired NSCLC patients with no brain metastases (NBMs). The EGFR mutation status of primary lesions was detected using the amplification refractory mutation system polymerase chain reaction. The BMs patients had a higher frequency of EGFR mutations than the NBMs patients (52.0 vs. 22.0% respectively, P

Aims The objective of this study was to investigate the role of plasma and platelet microRNAs in the occurrence of ischemic stroke in patients with diabetes mellitus. Methods miR-223, miR-146a, miR-495, and miR-107 expression in the plasma and platelets, blood glucose concentration, and platelet activation rate were measured in patients with diabetes mellitus and ischemic stroke, diabetes mellitus only, ischemic stroke only, and healthy controls. Platelet activity was measured by flow cytometric measurement of P-selectin expression, while miRNA was measured by real-time PCR. Results The expressions of platelet and plasma miR-223 and miR-146a were significantly downregulated in patients with ischemic stroke and diabetes mellitus or diabetes mellitus only, but not in patients with ischemic stroke only compared to healthy controls. The expressions of platelet and plasma miR-495 and miR-107 showed no significant differences among these four groups. The expression of platelet miR-223 and miR-146a significantly correlated with plasma miR-223 and miR-146a levels, blood glucose concentration, and platelet activation rate. Conclusions Hyperglycemia may downregulate the expressions of miR-223 and miR-146a, leading to subsequent platelet activation in patients with diabetes mellitus. Low platelet and plasma miR-223 and miR-146a expression is a risk factor for ischemic stroke in Chinese diabetes mellitus patients.

Increasing evidence suggests that intestinal bacteria play essential roles in cardiovascular disease (CVD). However, although the risk factors are similar to those of atherosclerosis, the profiles of the gut microbiome in individuals with cardiac valve calcification (VC) have not been investigated

The aim was to compare the efficacy and toxicity of paclitaxel plus platinum (TP) with gemcitabine plus platinum (GP) in untreated advanced non-small-cell lung cancer by a meta-analysis. An extensive literature search was performed for relevant randomized controlled trials. Studies were evaluated for eligibility and quality, and then the data were extracted and analyzed using Review Manager 5.1 software. Publication bias was evaluated according to Begg’s funnel plot and Egger’s test using Stata/SE version 10.1 software. Six randomized controlled trials including 2,793 patients were ultimately identified. The meta-analysis demonstrated that the efficacy was comparable between TP and GP regimens according to the pooled relative risks (RRs) for overall response rate [0.99, 95 % confidence interval (CI) = 0.88–1.13, p = 0.92], disease control rate (0.96, 95 % CI = 0.90–1.03, p = 0.24) and 1-year survival (0.99, 95 % CI = 0.90–1.09, p = 0.87), and the hazard ratios for overall survival (1.06; 95 % CI = 1.00–1.13, p = 0.07) and time-to-progression of disease (1.05, 95 % CI = 0.97–1.14, p = 0.20). Grade 3–4 nausea or vomiting, anemia and thrombocytopenia were less frequent in the TP group (RR = 0.53, 95 % CI = 0.35–0.78, p = 0.002; RR = 0.37, 95 % CI = 0.30–0.45, p

Symptomatic intracranial atherosclerotic stenosis (ICAS) and extracranial atherosclerotic stenosis (ECAS) are different in many aspects. Here, we explored the association between the location or severity of atherosclerotic stenosis and pro- or antiangiogenic factors, specifically vascular endothelial growth factor (VEGF) and endostatin (ES).We evaluated 198 consecutive patients with acute ischemia stroke: 132 with large-artery atherosclerosis (LAA) and 66 with small-artery occlusion (small-vessel occlusion). The LAA group was subclassified into 102 patients with ICAS and 30 with ECAS. Independent associations of VEGF, ES levels, and VEGF/ES ratio with the location of cerebral stenosis and the severity or short-term prognosis (14th day modified Rankin Scale) of ICAS were evaluated.Plasma concentrations of VEGF and ES were lower (P .05) in ICAS (38.07, 32.76-46.28 pg/mL and 58.95, 55.04-59.77 ng/mL) than those in ECAS (45.00, 34.30-83.34 pg/mL and 140.74, 85.63-231.21 ng/mL). Logistic regression analysis showed that VEGF concentrations and dyslipidemia were independently associated with ICAS, with odds ratios of .987 [95% CI = (.976, .998)] and .265 [95% CI = (.103, .792)], respectively. Moreover, plasmatic VEGF levels increased gradually along with the severity of ICAS (P = .003), and lower levels of ES (P = .040) or a higher VEGF/ES ratio (P = .048) were related to unfavorable short-term prognosis of ICAS.Lower VEGF levels are associated with the presence of symptomatic ICAS, but not with ECAS. Furthermore, the severity of ICAS is positively correlated with the levels of VEGF, and lower ES levels or a predominance of VEGF over ES are predictors of poor short-term prognosis of ICAS.

Purpose To study the clinical characteristics of patients with game-induced seizures in the Chinese population. Method We assessed 51 patients with various game-induced epileptic seizures. Based on whether they had spontaneous seizures, these 51 patients were classified as two groups. Twenty-seven patients who had both game-induced and spontaneous seizures were referred to as Group I, whereas twenty-four patients that had experienced seizures exclusively while playing specific games were assigned to Group II. All of the related clinical data of the patients was collected and evaluated. Results The patients in Group I presented with adolescent-onset and related to photosensitive idiopathic generalized epilepsy (IGE), were responsive to valproic acid (VPA) or magnesium valproate (VPA-Mg) therapy, and presented a major seizure-precipitating factor in response to electronic games. While patients in Group II were adult onset and not associated with IGE, showed uncertain responses to VPA and a benign prognosis, and presented major seizure-precipitating factors in response to non-electronic games. Conclusion There are obvious genetic differences between patients with game-induced epilepsy. It is necessary to differentiate between various types of game-induced seizures and select the corresponding treatment.

Cognitive deficits are a core feature of schizophrenia. Previous studies have shown that plasma asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, was increased in patients with schizophrenia. This study aimed to investigate the association of ADMA with cognitive deficits in schizophrenia. Forty-seven patients with schizophrenia and 45 healthy control subjects were recruited in present study. Cognitive function was assessed with a neuropsychological battery including 7 neurocognitive tests. Schizophrenic symptoms were assessed using the Positive and Negative Syndrome Scale and plasma ADMA concentration was measured by HPLC. We found that patients with schizophrenia exhibited poorer performances in nearly all of the cognitive tests except for the visual memory index compared with healthy controls. Plasma ADMA levels were significantly increased in patients with schizophrenia when compared to normal controls, and the mean ADMA concentration in patients with multiple episode schizophrenia was much higher than that of patients with first episode schizophrenia. For the patients, ADMA was negatively associated with attention, working memory and executive function in schizophrenia. These results suggest that ADMA may be involved in the pathophysiology of schizophrenia-associated cognitive impairments, and plasma ADMA could be a peripheral biomarker for evaluation of cognitive function in schizophrenia.

The aim of the study was to investigate the expression of miR-223 and FAM5C in the peripheral blood mononuclear cells (PBMCs) of cerebral infarction patients with or without diabetes. Sixteen cases with diabetes mellitus (DM), 14 cases with cerebral infarction (CI), 12 cases with cerebral infarction and diabetes mellitus (CIDM), and 18 healthy subjects were included in this study. Real-time PCR was used to quantify mRNA expression. Western blot was used to detect FAM5C protein level. Recombinant plasmids expressing miR-223-3p and 3' UTR of FAM5C were constructed. Dual-luciferase reporter system was used to analyze the binding of miR-223-3p to FAM5C 3' UTR. FAM5C mRNA and protein level were significantly higher in the PBMCs of CIDM patients compared with healthy controls (P

Brain metastasis as the first symptom of lung cancer is a unique clinical entity. We conducted a retrospective study to investigate the clinical characteristics and survival of patients with lung cancer whose first symptom was brain metastases in an Asian population.A retrospective study of 186 such patients who had been admitted to one institution in China between January 1, 2003 and December 30, 2008 was performed. The following data were collected and analyzed: manifesting signs and symptoms, imaging studies, extracerebral metastases, initial diagnosis, treatment, and patient survival.This sample population exhibited high rates of misdiagnosis upon initial presentation (46.8 %). Fifty-seven (30.6 %) patients presented with silent extracerebral metastases. Pathologies among this cohort varied, and adenocarcinomas were most commonly observed. Most patients received surgical resection, and some patients had additional whole-brain radiotherapy or stereotactic radiosurgery. The median survival time for the entire cohort was 15 months (95 % confidence interval, 12.9-17.1 months). Survival rates for 1, 2, and 5 years were 58.2, 34.2, and 6.5 %, respectively. The median survival time was 15, 14, 19, and 7 months for the gross total resection, incomplete resection, surgery + whole-brain radiotherapy, and surgery + stereotactic radiosurgery groups, respectively.Brain metastasis as the first symptom of lung cancer is a distinct clinical entity. Although overall survival was poor, combined treatments based on surgery for selected patients were reasonable with the exception of a minority who experienced long-term survival.

It is hypothesized that high expression of the excision repair cross-complementation group 1 (ERCC1) gene might be a positive prognostic factor, but predict decreased sensitivity to platinum-based chemotherapy. Results from the published data are inconsistent. To derive a more precise estimation of the relationship between ERCC1 and the prognosis and predictive response to chemotherapy of non-small cell lung cancer (NSCLC), a meta-analysis was performed. An electronic search of the PubMed and Embase database was performed. Hazard ratio (HR) for overall survival (OS) was pooled in early stage patients received surgery alone to analyze the prognosis of ERCC1 on NSCLC. HRs for OS in patients received surgery plus adjuvant chemotherapy and in patients received palliative chemotherapy and relative risk (RR) for overall response to chemotherapy were aggregated to analyze the prediction of ERCC1 on NSCLC. The pooled HR indicated that high ERCC1 levels were associated with longer survival in early stage patients received surgery alone (HR, 0.69; 95% confidence interval (CI), 0.58-0.83; P = 0.000). There was no difference in survival between high and low ERCC1 levels in patients received surgery plus adjuvant chemotherapy (HR, 1.41; 95% CI, 0.93-2.12; P = 0.106). However, high ERCC1 levels were associated with shorter survival and lower response to chemotherapy in advanced NSCLC patients received palliative chemotherapy (HR, 1.75; 95% CI, 1.39-2.22; P = 0.000; RR, 0.77; 95% CI, 0.64-0.93; P = 0.007; respectively). The meta-analysis indicated that high ERCC1 expression might be a favourable prognostic and a drug resistance predictive factor for NSCLC.

Myocardial metabolism and energy expenditure change during the process of heart failure, which also aggravate the pathophysiology of heart failure. It has been reported that intestinal microbe-generated metabolite trimethylamin N-oxide(TMAO) had a relationship with the development of cardiovascular

A meta-analysis of randomized controlled trials was performed to compare the efficacy, quality of life (QOL), symptom improvement and toxicities of gefitinib with docetaxel in previously treated advanced non-small-cell lung cancer.The PubMed database, the Cochrane Library and references of published trials were searched. Two reviewers independently assessed the quality of the trials and extracted data. The hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), relative risks (RRs) for overall response rate, QOL and symptom improvement, and odds ratios (ORs) for main toxicities were pooled using STATA package.Four multicenter, randomized controlled trials involving 2257 patients with previously treated advanced NSCLC were ultimately analyzed. The pooled HRs showed no significant difference in OS and PFS between the two groups (HR = 1.02, 95% CI = 0.92-1.12, p = 0.70; HR = 0.97, 95% CI = 0.88-1.07, p = 0.57, respectively). Gefitinib significantly improved overall response rate (RR = 1.58, 95% CI = 1.02-2.45, p = 0.04) and QOL (RR = 1.55, 95% CI = 1.27-1.88, p = 0.00 by Functional Assessment of Cancer Therapy-Lung and RR = 1.86, 95% CI = 1.43-2.42, p = 0.00 by Trial Outcome Index, respectively). Gefitinib had fewer grade 3 or 4 neutropenia and fatigue (OR = 0.02, 95% CI = 0.01-0.03, p = 0.00; and OR = 0.47, 95% CI = 0.32-0.70, p = 0.00, respectively), but more grade 3 or 4 rash (OR = 2.87, 95% CI = 1.24-6.63, p = 0.01) than docetaxel. The grade 3 or 4 nausea, vomiting and diarrhea and symptom improvement were comparable between the two drugs.In conclusion, although similar OS and PFS, gefitinib showed an advantage over docetaxel in terms of objective response rate, QOL and tolerability. Therefore, gefitinib is an important and valid treatment option for previously treated advanced non-small-cell lung cancer patients.

The recent studies show that the choline-derived metabolite trimethylamine N-oxide (TMAO) levels are associated with heart failure. Here, we test the hypothesis that TMAO induces oxidative injure in H9C2 cells through the suppression of AMP-activated kinase (AMPK)/ peroxisome-proliferator-activated

Purpose To compare the efficacy and toxicities of irinotecan/platinum (IP) with etoposide/platinum (EP) in patients with previously untreated extensive-stage small cell lung cancer (E-SCLC). Methods The PubMed database, the Cochrane Library, conference proceedings, databases of ongoing trials, and references of published trials and review articles were searched. Two reviewers independently assessed the quality of the trials and extracted data. The relative risk for overall response to treatment, hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios for the different types of toxicity were pooled by STATA package. Results Six trials involving 1476 patients with previously untreated E-SCLC were ultimately analyzed. The intention-to-treatment analysis indicated that IP regimens could acquire more overall response than EP regimens (relative risk=1.10, 95% confidence interval {lsqb;CI{rsqb;: 1.00–1.21, p = 0.043). The pooled HR showed that IP could prolong OS (HR = 0.81, 95% CI: 0.66–0.99, p = 0.044). Nevertheless, the pooled HR failed to show a favorable PFS in IP regimens (HR = 0.82, 95% CI: 0.64–1.06, p = 0.139). IP regimens led to less grade 3 to 4 anemia, neutropenia, and thrombocytopenia but more grade 3 to 4 vomiting and diarrhea than EP regimens. Treatment-related deaths were comparable between the two groups. Conclusion Although the PFS was similar from this meta-analysis, our results suggest that IP might have an advantage in overall response and OS compared with EP with less hematological toxicities. The IP regimens may be an alternative of EP regimens in the first-line treatment of E-SCLC.

Although some randomized controlled trials had compared the anti-CD20 monoclonal antibody rituximab plus chemotherapy (R-chemo) to chemotherapy alone for B-cell non-Hodgkin's lymphoma, the curative effects of R-chemo were still controversial. A systematic review and meta-analysis was performed to examine the efficacy of using R-chemo compared with the identical chemotherapy alone in the patients with B-cell non-Hodgkin's lymphoma.Medical databases and conference proceedings were searched for randomized controlled trials which compared R-chemo with chemotherapy alone in patients with newly diagnosed or relapsed B-cell non-Hodgkin's lymphoma. Endpoints were overall survival, overall response, disease control, and adverse events.Twelve eligible trials were identified, reporting outcomes of 4 996 patients. Fixed-effects analysis showed overall survival to be superior for R-chemo-treated patients (relative risks [RR], 1.09; 95%confidence interval [CI], 1.06-1.12, p0.00001). Superiority was also observed for the patients receiving R-chemo with respect to overall response (RR, 1.17; 95%CI, 1.10-1.25, p0.00001), complete response (RR, 1.52; 95%CI, 1.27-1.82, p0.00001), and disease control (RR, 1.36; 95%CI, 1.26-1.46, p0.00001). R-chemo improved overall survival, overall response and disease control in patients with diffuse large B-cell lymphoma (RR, 1.11, 95%CI: 1.06-1.16, p 0.0001; RR, 1.09, 95%CI: 1.01-1.19, p = 0.03 and RR, 2.00, 95%CI: 1.59-2.53, p0.00001, respectively) and follicular lymphoma (RR, 1.08, 95%CI: 1.04-1.12, p0.0001; RR, 1.19, 95%CI: 1.07-1.33, p = 0.001 and RR, 2.58, 95%CI: 1.61-4.12, p 0.0001, respectively). Meanwhile, R-chemo improved overall response in patients with mantle cell lymphoma (RR, 1.22, 95%CI: 1.07-1.40, p = 0.004).R-chemo is superior to chemotherapy alone in

Whether platinum plus gemcitabine or vinorelbine are equally effective in the treatment of advanced non-small-cell lung cancer (NSCLC) is still controversial, a meta-analysis was performed to compare the gemcitabine plus platinum with vinorelbine plus platinum regimens in first-line treatment of advanced NSCLC.A literature search was performed in PubMed database, the Cochrane Central Register of Controlled Trials (CENTRAL) database, the Physician Data Query (PDQ) database, EMBASE and the American Society of Clinical Oncology (ASCO) annual meeting abstracts. The following keywords were used: "non small cell lung cancer," or "Carcinoma, Non-Small-Cell Lung". Reference lists of original articles and review articles were also examined. The published languages and years were not limited. The trials searched were evaluated for eligibility and quality, and then the data were abstracted and analyzed. Endpoints were overall survival, overall response, and toxicity. Statistical tests for heterogeneity were one-sided; statistical tests for effect estimates were two-sided.Nine randomized controlled trials involving 2186 patients were identified from 453 reports. They were all published as full-text articles. The intention-to-treatment (ITT) analysis demonstrated that the patients with gemcitabine plus platinum regimens had an equal overall response rate in comparison with vinorelbine plus platinum regimens (RR, 0.91; 95%CI, 0.81-1.03; P=0.15). Furthermore, the 1-year survival rate for the two platinum-based regimens were comparable (RR, 1.06; 95%CI, 0.96-1.18; P=0.27). Subgroup analysis comparing the cisplatin plus gemcitabine or vinorelbine had achieved the same results. Vinorelbine plus platinum regimens led to more frequent grade 3 or 4 of neutropenia, nephrotoxicity, constipation and phlebitis (OR, 0.37; 95%CI, 0.26-0.52; P0.00001; OR, 0.38; 95%CI, 0.25-0.57; P0.00001; OR, 0.50; 95%CI, 0.27-0.92; P=0.03 and OR, 0.13; 95%CI, 0.05-0.32; P0.00001, respectively), while gemcitabine plus platinum chemotherapy inclined to developing more grade 3 or 4 thrombocytopenia (OR, 11.37; 95%CI, 4.56-28.38; P0.00001). The incidence of grade 3 or 4 anemia, nausea and vomiting were almost comparable between the two arms (OR, 1.12; 95%CI, 0.62-2.02; P=0.71 and OR, 0.72; 95%CI, 0.41-1.28; P=0.27, respectively). Similar results were also achieved in subgroup analyses between the gemcitabine and vinorelbine in combination with the cisplatin.It could be concluded that the efficacy were similar between the platinum plus gemcitabine or vinorelbine regimens. The choice of platinum plus gemcitabine or vinorelbine depends on the toxicity of the drugs and patients' tolerance.

Calcific aortic valve disease is one of leading cardiovascular diseases, and pharmacological intervention is currently unavailable. Increasing number of studies implicate aortic valve interstitial cells (AVICs) play a critical role in the pathogenesis of calcific aortic valve disease. IL-37 is

Purpose This study analyzed the clinicopathologic characteristics of typical medullary breast carcinoma (TMBC) in a cohort of Chinese patients. Methods We conducted a retrospective review of clinical data including general information, pathologic results, treatment regimens, and patient survival in cases of TMBC diagnosed between February 2004 and April 2011. Results A total of 117 patients were enrolled, with a median age of 52 years (range, 28∼92 years). Stage I and II disease accounted for 31.6% and 61.6% of the cases, respectively. Hormonal receptor negative disease (estrogen receptor negative, 68.4%; progestogen receptor negative, 86.3%) was more prevalent in this population. Human epidermal growth factor receptor-2 (HER-2) positivity was 20.5%, while equivocal and HER-2 negative cases represented 16.2% and 63.2% of the cohort. The triple-negative, luminal, and HER-2 overexpressing subtypes constituted 44.4%, 31.6%, and 15.4% of the cases, respectively. The various TMBC subtypes showed no differences regarding tumor size, rates of lymph node(s) metastasis, TNM staging, treatment regimens, and 2-year recurrence rates. However, patients with triple-negative disease were more likely to be younger, when compared to those with luminal disease (P = 0.002). At a median follow-up of 56 months (range, 2–112 months), the 2-year disease-free survival and overall survival rates were 99.1% and 98.2%, respectively. Conclusion Early stage disease dominated the study cohort, and at two years after surgery, recurrence was extremely low. The heterogeneity of molecular subtypes was clearly shown, and no apparent differences were found among the clinicopathologic characteristics of the triple-negative, luminal, and HER-2 overexpressing subtypes.

Although calcific aortic stenosis is common, calcification of the other three heart valves is not. The aortic valve interstitial cell (VIC) has been implicated in the pathogenesis of aortic stenosis. Proinflammatory stimulation of aortic VICs induces an osteogenic and inflammatory phenotypic change. We hypothesized that the VICs of the other heart valves do not undergo these changes. Using isolated human VICs from normal aortic, mitral, pulmonary, and tricuspid valves, our purpose was to compare the osteogenic response to proinflammatory stimulation via toll-like receptor 4 (TLR-4).Aortic, pulmonic, mitral, and tricuspid (n=4 for each valve type) VICs were isolated from hearts valves explanted from patients undergoing cardiac transplantation. Cells were cultured and grown to confluence in passage 2-6 before treatment with Lipopolysaccharide (LPS) (100-200 ng/mL) for 24 or 48 h. Cells were characterized by immunofluorescent staining. TLR-4 expression was analyzed (immunoblotting, flow cytometry). Bone morphogenetic protein 2 and intercellular adhesion molecule 1 production were determined (immunoblotting). Monocyte chemoattractant protein 1 levels were determined by enzyme-linked immunosorbent assay. Statistics were by Mann-Whitney U test.TLR-4 stimulation induced bone morphogenetic protein 2 production only in aortic VICs (P0.05). Intra-cellular adhesion molecule 1 production and monocyte chemoattractant protein 1 secretion increased in a similar fashion among TLR-4-stimulated VICs from all four valves.Proinflammatory stimulation induces an osteogenic phenotype in aortic VICs but not mitral, pulmonic, or tricuspid VICs. We conclude that this differential osteogenic response of aortic VICs contributes to the pathogenesis of calcific aortic stenosis.