Alterations in Serum Lipids and Lipoproteins Induced by Neoadjuvant Chemotherapy in Patients with Osteosarcoma around the Knee Joint: A Retrospective Analysis.

OBJECTIVE: To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy. METHODS: After retrospectively screening the data of 742 patients between January 2007 and July 2020, 50 patients aged 13 to 39 years with Enneking stage II disease were included in the study. Serum lipid levels, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein-α [Lp(a)], and apolipoprotein A1, B, and E (ApoA1, ApoB, and ApoE), and clinicopathological characteristics were collected before and after neoadjuvant chemotherapy. RESULTS: The mean levels of TC, TG, and ApoB were significantly increased following neoadjuvant chemotherapy (16%, 38%, and 20%, respectively, vs. pretreatment values; P<0.01). The mean levels of LDL-C and ApoE were also 19% and 16% higher, respectively (P<0.05). No correlation was found between the pretreatment lipid profile and the histologic response to chemotherapy. An increase in Lp(a) was strongly correlated with the Ki-67 index (R=0.31, P=0.023). Moreover, a trend toward longer disease-free survival (DFS) was observed in patients with decreased TG and increased LDL-C following chemotherapy, although this difference was not statistically significant (P=0.23 and P=0.24, respectively). CONCLUSION: Significant elevations in serum lipids were observed after neoadjuvant chemotherapy in patients with localized osteosarcoma. There was no prognostic significance of pretreatment serum lipid levels on histologic response to neoadjuvant chemotherapy. The scale of increase in serum Lp(a) might have a potential prognostic role in osteosarcoma. Patients with increased LDL-C or reduced TG after chemotherapy seem to exhibit a trend toward favorable DFS.

The Relationship between Beverages Consumption and Cognitive Impairment in Middle-Aged and Elderly Chinese Population.

Some evidence shows that beverage consumption has an impact on cognitive performance. This is a follow-up study of dietary habits and cognitive function in the Chinese middle-aged and elderly population. The objective of this study was to explore the relationship between beverage consumption and cognitive impairment. The source and grouping of the participants can be seen in the previous article, "Study of Diet Habits and Cognitive Function in the Chinese Middle-Aged and Elderly Population: The Association between Folic Acid, B Vitamins, Vitamin D, Coenzyme Q10 Supplementation and Cognitive Ability". Among 892 participants, one-third (296) completed both Amyloid beta(Aß)-PET and plasma biomarkers. The results showed that the consumption of beverages (green tea, coffee, pure milk) was a protective factor for cognitive impairment, daily water consumption <1500 mL (especially <500 mL) was a risk factor for cognitive impairment, and the above correlated with baseline cognitive status. The relationship of green tea, coffee, and pure milk consumption with cognitive impairment was related to gender. We also found that among the participants with Aß deposition, the consumption of pure milk and green tea was associated with low levels of p-Tau-181. In conclusion, the relationship between beverage consumption and cognitive impairment in Chinese middle-aged and elderly adults may be related to baseline cognitive status, gender, and Aß deposition.

Study of Diet Habits and Cognitive Function in the Chinese Middle-Aged and Elderly Population: The Association between Folic Acid, B Vitamins, Vitamin D, Coenzyme Q10 Supplementation and Cognitive Ability.

A growing body of evidence suggests that vitamin supplements play a role in the prevention of cognitive decline. The objective of the present cross-sectional study was to evaluate the relationship between cognitive ability and folic acid, B vitamins, vitamin D (VD) and Coenzyme Q10 (CoQ10) supplementation. The sample consisted of 892 adults aged above 50 who were assessed for their cognitive status in the Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (China) from July 2019 to January 2022. According to the degree of cognitive impairment, the subjects were divided into a normal control (NC) group, subjective cognitive decline (SCD) group, mild cognitive impairment (MCI) group and Alzheimer's disease (AD) group. The results indicated a lower risk of AD in the daily VD-supplemented subjects with MCI compared to those who were not supplemented; a lower risk of cognitive impairment in those with normal cognitive who consumed VD, folic acid or CoQ10 on a daily basis compared those who did not; and a lower risk of cognitive impairment in subjects with normal cognitive performance who consumed B vitamin supplements, either daily or occasionally, compared to those who did not. The correlation was independent of other factors that potentially affect cognition, such as education level, age, etc. In conclusion, our findings confirmed a lower prevalence of cognitive impairment in those who took vitamins (folic acid, B vitamins, VD, CoQ10) daily. Therefore, we would recommend daily supplementation of vitamins (folic acid, B vitamins, VD, CoQ10), especially group B vitamins, as a potential preventive measure to slow cognitive decline and neurodegeneration in the elderly. However, for the elderly who have already suffered from cognitive impairment, VD supplementation may also be beneficial for their brains.

Waist-to-height ratio is a simple and practical alternative to waist circumference to diagnose metabolic syndrome in type 2 diabetes.

Background: As an indicator of abdominal obesity, waist circumference (WC) varied with race and gender in diagnosing metabolic syndrome (MetS). Therefore, it is clinically important to find an alternative indicator of abdominal obesity independent of these factors to diagnose MetS. Our aims were to evaluate the association between waist-to-height ratio (WHtR) and MetS and further determine whether WHtR could be used as a simple and practical alternative to WC to diagnose MetS in patients with type 2 diabetes mellitus (T2DM). Methods: This cross-sectional, real-world study recruited 8488 hospitalized T2DM patients including 3719 women (43.8%) aged from 18 to 94 years and 4769 men (56.2%) aged from 18 to 91 years. A WHtR cut-off of 0.52 was used to diagnose MetS in both men and women T2DM patients based on our previous study. The association of WHtR with MetS in T2DM patients was analyzed by binary logistic regression. The consistency of two diagnostic criteria for MetS according to WC and WHtR was determined by Kappa test. Results: The prevalence of MetS according to WHtR was 79.4% in women and 68.6% in men T2DM patients, which was very close to the prevalence of MetS according to WC in both women (82.6%) and men (68.3%). The prevalence of MetS diagnosed by WC in both men and women with WHtR ≥ 0.52 was significantly higher than in those with WHtR < 0.52 after adjustment for age and duration of diabetes (89.2 vs. 38.7% for men; 92.8 vs. 57.4% for women; respectively, all p < 0.001). Binary logistic regression analysis displayed that after adjusting for confounding factors, WHtR was significantly associated with the presence of MetS in both men and women (men: OR = 4.821, 95% CI: 3.949-5.885; women: OR = 3.096, 95% CI: 2.484-3.860; respectively, all p < 0.001). Kappa test revealed that there was an excellent consistency between the diagnosis of MetS based on WC and on WHtR in T2DM patients (men: kappa value = 0.929, 95% CI: 0.918-0.940; women: kappa value = 0.874, 95% CI: 0.854-0.894; total: kappa value = 0.911, 95% CI: 0.901-0.921; respectively, all p < 0.001). Conclusion: WHtR is independently associated with the presence of MetS and can be used as a simple and practical alternative to WC to diagnose MetS regardless of gender in T2DM patients.

Fibrinogen-Albumin Ratio Index Exhibits Predictive Value of Neoadjuvant Chemotherapy in Osteosarcoma.

Purpose: Inflammatory response and nutritional status are associated with cancer development and progression. The present study aimed to evaluate the predictive ability of the fibrinogen-albumin ratio index (FARI) to the efficacy of neoadjuvant chemotherapy (NAC) for osteosarcoma. Patients and methods: A retrospective analysis involving 752 consecutive osteosarcoma patients between 2012 and 2020 was performed. Data on serum fibrinogen, albumin levels, white blood cell count, platelet count, and alkaline phosphatase (ALP) before and after NAC were collected. The predictive value of the NAC efficacy in osteosarcoma was assessed by constructing a receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Prognosis and its predictive factors were analyzed by Kaplan-Meier method and COX regression analysis. Nomogram was established according to selected variables. The predictive performance of the nomogram model was assessed using C-statistics. Results: A total of 203 patients were included. ROC analysis showed that both FARI before NAC (preFARI; AUC = 0.594, p = 0.032) and the change in FARI before and after NAC (dfFARI = preFARI-postFARI; AUC = 0.652, p = 0.001) exhibited more favorable predictive ability than ALP and other inflammation markers. The preFARI was divided into the high group (>6.1%) and the low group (≤6.1%) based on the optimal cut-off value of 6.1%. Patients with a high preFARI showed significantly decreased metastasis-free survival (MFS) and disease-free survival (DFS) (all p<0.01). In multivariable analysis, preFARI was an independent prognostic marker for patients with osteosarcoma. Predictive nomograms exhibited good ability to predict MFS (C-index = 0.748, se = 0.028) and DFS (C-index=0.727, se = 0.030). Conclusion: Our findings indicated that FARI exhibits the favorable predictive ability for the efficacy of NAC for osteosarcoma, which could support clinicians and patients in clinical decision-making and treatment optimization.

Serum 25-hydroxy vitamin D level is associated with cognitive impairment in people aged 65 years and older.

BACKGROUND: Vitamin D deficiency is prevalent in the population, especially in older people. In recent years, studies have revealed an association between a low vitamin D level and cognitive decline. The present research aimed to investigate the relationship of serum 25-hydroxyvitamin D (25-OH-D) level with cognitive function in senior patients. METHODS: We recruited 299 patients aged 65 years and older. The patients were grouped based on their serum 25-OH-D levels into group A (<10.0 ng/mL), B (10.0-19.9 ng/mL), and C (≥20.0 ng/mL). Cognitive function was assessed with the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating (CDR) scale, and Activities of Daily Living (ADL) scale. RESULTS: MMSE and MoCA scores were significantly lower in group A (26.02±3.99 and 21.56±5.59, respectively) than in group B (27.34±2.79 and 23.94±4.74, respectively) and group C (27.65±2.54 and 24.95±4.45, respectively). The proportion of patients with cognitive impairment was increased in group A (71.1%) compared to group B (55.3%) and group C (43.9%), and the difference was statistically significant (both P<0.01). Spearman's correlation analysis showed that MMSE and MoCA had a positive relationship with serum 25-OH-D level (ß=0.173 and 0.243, both P<0.01) with adjustments for factors as age, sex, and education level. Stepwise regression analysis indicated that MMSE and MoCA scores were correlated with serum 25-OH-D level, age, and education level. CONCLUSIONS: A lower level of 25-OH-D is common in senior patients and is associated with cognitive impairment. Patients with severe deficiency of vitamin D (serum 25-OH-D level <10 ng/mL) have lower MMSE and MoCA scores and a higher risk of cognitive dysfunction.

DSN1 is a prognostic biomarker and correlated with clinical characterize in breast cancer.

DSN1 affects cell cycle progression and is associated with clinical-pathological features in colorectal and hepatocellular carcinomas. However, the biological function of DSN1 in breast cancer is still indistinct. In this study, we comprehensively analyzed the correlation between DSN1 expression in different molecular subtypes or stages of breast cancer and investigated the prognostic value of DSN1 in databases such as Oncomine, Cancer Cell Line Encyclopedia, UALCAN, Human Protein Atlas, Kaplan-Meier Plotter, OncoLnc, GEPIA. Moreover, we investigated the correlation of DSN1 with tumor-infiltrating immune cells in the different tumor microenvironments via Tumor Immune Estimation Resource database and explore DSN1 co-expression networks in breast cancer via LinkedOmics analysis, NetworkAnalyst database analysis. Finally, we also performed our immunohistochemical experiments to explore the expression of DSN1 in different stages or subtypes of breast cancer. The findings in this article shed light on the essential role of DSN1 in breast cancers as well as suggested that the upregulation of DSN1 expression was strongly associated with poor prognosis and decreased survival in breast cancer, and there were significant differences in its expression in different pathological subtypes and stages of breast cancer.

Autophagy of macrophages is regulated by PI3k/Akt/mTOR signalling in the development of diabetic encephalopathy.

The development of diabetic encephalopathy (DE) is enhanced by inflammatory macrophages, and is suppressed by macrophage autophagy. However, the molecular signaling that controls macrophage autophagy in DE remains ill-defined. Here, DE is induced in rats that received intraperitoneal injection of streptozotocin (STZ). In macrophages isolated from the brain of the rats, we detected downregulated autophagy activity and enhanced PI3k/Akt/mTOR/S6K1 signaling. In order to examine the role of autophagy and PI3k/Akt/mTOR signaling in DE development, an mTOR inhibitor, rapamycin, or an autophagy inhibitor, chloroquine (CQ), were administered to the rats that that received STZ. We found that rapamycin significantly enhanced DE development through mTOR suppression-induced augmentation of macrophage autophagy, while CQ significantly decreased DE development through suppression of macrophage autophagy. Together, our data suggest that PI3k/Akt/mTOR signaling may promote the development of DE through suppression of macrophage autophagy.

Cathepsin L deficiency results in reactive oxygen species (ROS) accumulation and vascular cells activation.

Recent evidence suggests a link between cathepsin L (CTSL) and vascular diseases. However, its contribution to reactive oxygen species (ROS) homeostasis in the vasculature remains unknown. p66shc is a redox enzyme implicated in mitochondrial ROS generation and translation of oxidative signals. In this study, we explored the relationship between CTSL and oxidative damage in vasculature and whether the oxidative damage is mediated by p66shc.Carotid arteries from aged mice (24 months old) showed a reduction in CTSL expression compared with young wild-type mice (4 months old). Local knockdown of CTSL in carotid arteries of young mice by adenoviral vector encoding the short hairpin RNA targeting CTSL leading to premature vascular aging, as shown by mitochondrial disruption, increased ß-galactosidase-positive cells, reduced telomerase activity, and up-regulation of p66shc. Knockdown of CTSL decreased the expression of mitochondrial oxidative phosphorylation (OXPHOS) complexes I, III, and IV, leading to increased mitochondrial ROS and hyperpolarization of the mitochondrial membrane in vitro. Furthermore, knockdown of CTSL also stimulated ROS production and senescence in vascular cells, accompanied by the up-regulation of p66shc.However, p66shc knockdown blunted the alteration in ROS production, and senescence in CTSL knockdown vascular cells. This study suggests that CTSL knockdown partially induces vascular cells damage via increased ROS production and up-regulation of p66shc.

Neutrophil CD64 as a Marker of Bacterial Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are responsible for most mortality in patients with chronic obstructive pulmonary disease (COPD) and are caused mainly by bacterial infection. We analyzed and compared neutrophil CD64 expression (using the ratio of CD64 level in neutrophils to that in lymphocytes as an index), serum C-reactive protein (CRP), procalcitonin (PCT) levels, white blood cell (WBC) count, and neutrophil percentage among healthy subjects and patients with stable COPD or AECOPD. Compared with patients with COPD and healthy subjects, patients with AECOPD demonstrated significantly increased CD64 index, CRP, PCT, WBC count, and neutrophil percentage. Interestingly, CD64 index and PCT were both significantly higher in patients with AECOPD with positive bacterial sputum culture than those with negative culture. Furthermore, CD64 index and PCT were positively correlated in AECOPD, and there was also correlation between CD64 index and CRP, WBC, and neutrophil percentage. These data suggest that CD64 index is a relevant marker of bacterial infection in AECOPD. We divided patients with AECOPD into CD64-guided group and conventional treatment group. In CD64-guided group, clinicians prescribed antibiotics based on CD64 index; while in the conventional treatment group, clinicians relied on experience and clinical symptoms to determine the necessity for antibiotics. We found that the efficacy of antibiotic treatment in CD64-guided group was significantly improved compared with the conventional treatment group, including reduction of hospital stays and cost and shortened antibiotic treatment duration. Thus, the CD64 index has important diagnostic and therapeutic implications for antibiotic treatment of patients with AECOPD.

Percutaneous Vertebroplasty Versus Conservative Treatment in Aged Patients With Acute Osteoporotic Vertebral Compression Fractures: A Prospective Randomized Controlled Clinical Study.

STUDY DESIGN: A prospective randomized clinical trial. OBJECTIVE: In this study, we determine whether percutaneous vertebroplasty (PVP) offers extra benefits to aged patients with acute osteoporotic vertebral compression fractures (OVCFs) over conservative therapy (CV). SUMMARY OF BACKGROUND DATA: OVCFs are common in the aged population with osteoporosis. While the optimal treatment of aged patients with acute OVCFs remains controversial, PVP, a minimally invasive procedure, is a treatment option to be considered. METHODS: Patients aged at 70 years or above with acute OVCF and severe pain from minor or mild trauma were assigned randomly to PVP and CV groups. The primary outcome was pain relief as measured by VAS score in 1-year follow-up period. The second outcome was quality of life assessed with ODI and Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO). Patient satisfaction surveys were also recorded. RESULTS: A total of 135 patients were enrolled, and 107 (56 in PVP group; 51 in CV group) completed 1-year follow-up. In PVP group, the vertebroplasty procedure was performed at a mean of 8.4 ±â€Š4.6 days (range, 2-21 days) after onset. Vertebroplasty resulted in much greater pain relief than did conservative treatment at postoperative day 1 (P < 0.0001). At every time point of follow-up, pain relief and quality of life were significantly improved in PVP group than in CV group at 1 week, 1 month, 3 months, 6 months, and 1 year (all P < 0.0001). The final follow-up surveys indicated that patients in PVP group were significantly more satisfied with given treatment (P < 0.0001). In addition, lower rate of complications was observed in PVP group (P < 0.0001). CONCLUSION: In aged patients with acute OVCF and severe pain, early vertebroplasty yielded faster, better pain relief and improved functional outcomes, which were maintained for 1 year. Furthermore, it showed fewer complications than conservative treatment. LEVEL OF EVIDENCE: 2.

Procalcitonin guidance for reduction of antibiotic use in patients hospitalized with severe acute exacerbations of asthma: a randomized controlled study with 12-month follow-up.

INTRODUCTION: Patients with severe acute exacerbations of asthma often receive inappropriate antibiotic treatment. We aimed to determine whether serum procalcitonin (PCT) levels can effectively and safely reduce antibiotic exposure in patients experiencing exacerbations of asthma. METHODS: In this randomized controlled trial, a total of 216 patients requiring hospitalization for severe acute exacerbations of asthma were screened for eligibility to participate and 169 completed the 12-month follow-up visit. Patients were randomized to either PCT-guided (PCT group) or standard (control group) antimicrobial therapy. In the control group, patients received antibiotics according to the attending physician's discretion; in the PCT group, patients received antibiotics according to an algorithm based on serum PCT levels. The primary end point was antibiotic exposure; secondary end points were clinical recovery, length of hospital stay, clinical and laboratory parameters, spirometry, number of asthma exacerbations, emergency room visits, hospitalizations and need for corticosteroid use due to asthma. RESULTS: PCT guidance reduced antibiotic prescription (48.9% versus 87.8%, respectively; P < 0.001) and antibiotic exposure (relative risk, 0.56; 95% confidence interval, 0.44 to 0.70; P < 0.001) compared to standard therapy. There were no significant differences in clinical recovery, length of hospital stay or clinical, laboratory and spirometry outcomes in both groups. Number of asthma exacerbations, emergency room visits, hospitalizations and need for corticosteroid use due to asthma were similar during the 12-month follow-up period. CONCLUSION: A PCT-guided strategy allows antibiotic exposure to be reduced in patients with severe acute exacerbation of asthma without apparent harm. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR-TRC-12002534 (registered 26 September 2012).

Effects of combination therapy with levamlodipine and bisoprolol on stroke in rats.

AIM: To examine the effects of combination with levamlodipine and bisoprolol on stroke in rats. METHODS: For acute study, Systolic blood pressure (SBP) and heart period (HP) were monitored in conscious stroke prone-spontaneously hypertensive rats (SHR-SP) and sinoaortic denervation (SAD) rats before and after intragastric administration of either drug at a single dose. Rats were subjected to middle cerebral arterial occlusion (MCAO) half an hour after drug administration; sacrificed 24 h later to measure the infarct size. For long-term study, drugs (either alone or in combination) were delivered via food to SHR-SP. The survival time was recorded. RESULTS: SBP was significantly reduced by combination therapy both in SHR-SP and SAD rats. Neutralization on heart rate (HR) was observed in combination. The drug combination increased baroreflex sensitivity (BRS) and reduced SBP variability (SBPV). In chronic experiments, the lifespan of SHR-SP rats exposed to the drug combination was longer than that in rats exposed to either drug alone. The infarct area was the smallest in subjects receiving drug combination in SD rats both with and without SAD. CONCLUSION: Combined use of levamlodipine and bisoprolol produced better protection against stroke.

Inhibition of NF-kappaB activation by Pyrrolidine dithiocarbamate partially attenuates hippocampal MMP-9 activation and improves cognitive deficits in streptozotocin-induced diabetic rats.

Matrix metalloproteinase-9 (MMP-9) has been found at significantly increased activity and also contributes to blood-brain barrier degradation in diabetes. Activation of NF-κB pathway is associated with diabetes-induced cognitive impairment, and MMP-9 gene promoter contains a highly conserved motif that matches the NF-κB p65 binding element. No data have been yet provided to show that diabetes-induced cognitive decline is actually associated with increased activity of MMP-9, however, so we sought to understand the potential role of NF-κB-MMP-9 pathway in diabetic rats' brain. Streptozocin (STZ) was used to induce diabetes in Wistar rats. Pyrrolidine dithiocarbamate (PDTC), an effective NF-κB inhibitor, was administrated to diabetic rats for 6 weeks from the end of diabetes induction. Six weeks later, separate cohorts of rats were tested for cognitive function with Morris water maze task, or euthanized to assess MMP-9 and NF-κB levels in hippocampus. The diabetic rats developed cognitive deficit which was associated with enhanced hippocampal MMP-9 and NF-κB expression. PDTC treatment returned the levels of NF-κB toward their control values and significantly improved diabetes-induced behavioral dysfunction. However, the hippocampal MMP-9 expression triggered by diabetes was only slightly (though significantly) attenuated because MMP-9 protein level in PDTC treated diabetic rats was still higher than that in control rats. Moreover, chronic PDTC treatment did not affect the body weight and plasma glucose levels as compared to the diabetic group, which suggested that PDTC could not ameliorate the diabetic metabolic disorder. In conclusion, these data reveal that diabetes-associated cognitive deficit stems partially from up-regulation of hippocampal MMP-9 via activation of NF-κB signaling pathway.

The relationship between insulin resistance and osteoporosis in elderly male type 2 diabetes mellitus and diabetic nephropathy.

OBJECTIVE: Diabetes is often associated with complications and comorbidities. Diabetic osteoporosis (OP) is increasingly recognized as a significant comorbidity of type 2 diabetes mellitus (T2-DM). In this study, we intended to determine whether type 2 diabetes was associated with a higher bone mineral density (BMD) in older males, and investigate the related risk factors of diabetes mellitus accompanied with OP. MATERIALS AND METHODS: To assess the effects of diabetes and its complications on the risk of bone fractures, the daily glycemia, insulin and HbAlc of T2-DM patients were detected. At the same time, Dual Energy X-ray Absorptiometry (DEXA) was used to measure the BMD of whole body, lumbar spine and proximal femoral at 2-year intervals. RESULTS: The BMD in elderly male patients suffered from T2-DM was associated with kidney function. The decrease of BMD in elderly male patients with T2-DM was related to HbA1c and body mass index (BMI). The BMD in group of renal function insufficiency or clinical albuminuria which are closely related with insulin insufficiency were much lower than that in the group of normal control. Additionally, a significantly lower (P<0.05) T-score was found in patients with nephropathy as compared with those without the complications. CONCLUSION: The elderly patients with type 2 diabetes mellitus are prone to develop OP. The insufficiency of insulin, the decreased insulin sensitivity and diabetic nephropathy are important causes for OP in the patients with type 2 diabetes.

Effects of telmisartan on insulin resistance and visceral fat distribution in Chinese hypertensive patients with obesity.

OBJECTIVE: To investigate the effects of telmisartan on body fat distribution and insulin sensitivity in patients with hypertension and obesity. METHODS: In this prospective, randomized study, outpatients from the Sixth People's Hospital affiliated to Shanghai Jiaotong University, Shanghai, China were treated with telmisartan (n=23), or losartan (n=22) for 16 weeks between December 2009 to January 2011. Parameters such as waist and hip circumference, body mass index, fasting blood glucose, insulin, lipids, serum adiponectin, and tumor necrosis factor-alpha (TNF-alpha) were measured before and after treatment. The abdominal visceral fat area (VFA) and subcutaneous fat area (SFA) were determined by magnetic resonance imaging. Insulin sensitivity was estimated by homeostasis model assessment (HOMA-IR). RESULTS: Compared with baseline, the systolic and diastolic blood pressure decreased significantly in both groups. However, the levels of HOMA-IR, serum adiponectin, and TNF-alpha only improved in the telmisartan group. Similarly, the VFA was reduced in the telmisartan group, while the SFA did not change in either group. CONCLUSION: Telmisartan improves both hemodynamic and metabolic abnormalities found in hypertensive patients with obesity. The additional benefits may be partly due to visceral fat remodeling.

MicroRNA-1 regulates cardiomyocyte apoptosis by targeting Bcl-2.

MicroRNA-1 (miR-1) is preferentially expressed in cardiac muscles, and the expression has been demonstrated to be involved in cardiac development and cardiovascular diseases. Here we report that miR-1 is closely related with ischemia/reperfusion injury in a rat model. The level of miR-1 is inversely correlated with Bcl-2 protein expression in cardiomyocytes of the I/R rat model. In vitro, the level of miR-1 was dramatically increased in response to H(2)O(2). Overexpression of miR-1 facilitated H(2)O(2)-induced apoptosis in cardiomyocytes. Inhibition of miR-1 by antisense inhibitory oligonucleotides caused marked resistance to H(2)O(2). Through bioinformatics, we identified the potential target sites for miR-1 on the 3' UTR of Bcl-2. miR-1 significantly reduced the expression of Bcl-2 in the levels of mRNA and protein. The post-transcriptional repression of Bcl-2 was further confirmed by luciferase reporter experiments. These data demonstrated that miR-1 plays an important role in the regulation of cardiomyocyte apoptosis, which is involved in post-transcriptional repression of Bcl-2.

[Efficacy and safety of azosemide in patients with edema and ascites].

OBJECTIVE: To assess the efficacy and safety of azosemide in patients with edema and ascites. METHODS: A multicentral, randomized, double-blind, controlled clinical trial was applied. All 223 patients (cardiac edema 92, hepatogenic edema 63, renal edema 68) were randomized to azoesmide and furosemide group, and all patients were treated for 2 weeks. Patients with cardiac or renal edema took azosemide (30 mg/d) or furosemide (20 mg/d); patients with hepatogenic edema took azosemide (60 mg/d) or furosemide (40 mg/d). The dosage were adjusted to azosemide 60 mg/d (cardiac, renal edema), 90 mg (hepatogeic edema); or furosemide 40 mg/d (cardiac, renal edema), 60 mg (hepatogeic edema), if diuretic effects were not obtained at the end of third day. RESULTS: At the end of the study, the weight changes were (2.87+/-3.10) kg and (2.81 +/-2.84) kg; the total effective rate of edema lessen was 89.19% and 89.81%; the total effective rate of heart function improvement was 64.44% and 66.66%; the 24 h urine output increased (321.85 +/-669.52) ml and (273.80 +/-645.72) ml for azosemide and furosemide, respectively. The total effective rate of ascites lessen (tested by B-ultrasound) was 89.28% and 86.66%; abdominal girth decreased (5.20 +/-3.58) cm and (5.03 +/-3.74) cm for azosemide and furosemide, respectively. The adverse event rate was 23.01% in azosemide group and 21.01% in furosemide group; the main adverse effects were hypokalemia, hyperuricemia, hypertriglyceridemia and thirsty. CONCLUSION: Azosemide could effectively lessen edema, improve heart function and decrease ascitesûit is well tolerated and is particularly useful for the diuretic treatment.

Losartan inhibited expression of matrix metalloproteinases in rat atherosclerotic lesions and angiotensin II-stimulated macrophages.

AIM: To explore whether the angiotensin II (Ang II) receptor 1 (AT1) antagonist, losartan could reduce activity and expression of matrix metalloproteinases (MMPs) in rat atherosclerotic plaques. METHODS: Male Wistar-Kyoto rats were ip injected a single dose of vitamin D3 600 kU x kg(-1) x month(-1) and fed an atherogenic diet for 4 months to induce experimental atheroma. Then either placebo or losartan 50 mg x kg(-1) x d(-1) was administered in rats for another 2 months. In vitro, the effect of losartan 0.1-10 micromol/L on the expression of MMP-2 and MMP-9 was investigated in Ang II-stimulated rat peritoneal macrophages. The expression and activity of MMP-2 and MMP-9 were monitored by Western blot, RT-PCR, and SDS-PAGE zymography analysis. RESULTS: High levels of MMP-2 and MMP-9 were expressed in rat atherosclerotic lesions. Losartan significantly reduced the activity and expression of MMP-2 and MMP-9 compared with the placebo group (MMP-2, 5861+/-539 vs 8991+/-965, P<0.05; MMP-9,10527+/-1002 vs 14623+/-2462, P<0.01). In cultured rat peritoneal macrophages, Ang II 0.1 micromol/L elicited an increase in MMP-2 and MMP-9 activity and expression that were prevented by losartan in a dose-dependent manner (P<0.01). But the AT2 receptor antagonist PD123319 had no effect. CONCLUSION: Losartan reduced the expression and activity of MMP-2 and MMP-9 in rat atherosclerotic lesions. The anti-atherogenic effects of losartan were due to the direct inhibition of Ang II bioactivity.