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.

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.

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.

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.

[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.