Development of a Multiplexed Liquid Chromatography Multiple-Reaction-Monitoring Mass Spectrometry (LC-MRM/MS) Method for Evaluation of Salivary Proteins as Oral Cancer Biomarkers.

Multiple (selected) reaction monitoring (MRM/SRM) of peptides is a growing technology for target protein quantification because it is more robust, precise, accurate, high-throughput, and multiplex-capable than antibody-based techniques. The technique has been applied clinically to the large-scale quantification of multiple target proteins in different types of fluids. However, previous MRM-based studies have placed less focus on sample-preparation workflow and analytical performance in the precise quantification of proteins in saliva, a noninvasively sampled body fluid. In this study, we evaluated the analytical performance of a simple and robust multiple reaction monitoring (MRM)-based targeted proteomics approach incorporating liquid chromatography with mass spectrometry detection (LC-MRM/MS). This platform was used to quantitatively assess the biomarker potential of a group of 56 salivary proteins that have previously been associated with human cancers. To further enhance the development of this technology for assay of salivary samples, we optimized the workflow for salivary protein digestion and evaluated quantification performance, robustness and technical limitations in analyzing clinical samples. Using a clinically well-characterized cohort of two independent clinical sample sets (total n = 119), we quantitatively characterized these protein biomarker candidates in saliva specimens from controls and oral squamous cell carcinoma (OSCC) patients. The results clearly showed a significant elevation of most targeted proteins in saliva samples from OSCC patients compared with controls. Overall, this platform was capable of assaying the most highly multiplexed panel of salivary protein biomarkers, highlighting the clinical utility of MRM in oral cancer biomarker research.

The survival impact of delayed surgery and adjuvant chemotherapy on stage II/III rectal cancer with pathological complete response after neoadjuvant chemoradiation.

Neoadjuvant concurrent chemoradiation (CCRT) is standard treatment for clinical stage II/III rectal cancers. However, whether patients with pathological complete response (pT0N0, pCR) should receive adjuvant chemotherapy and whether delayed surgery will influence the pCR rate remains controversial. A nationwide population study was conducted using the Taiwan Cancer Registry Database from January 2007 to December 2013. Kaplan-Meier survival analysis was performed. Cox proportional hazards models were used to estimate multivariate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). Of the 1,914 patients who received neoadjuvant CCRT, 259 (13.6%) achieved pCR and had better survival (adjusted HR: 0.37, 95% CI: 0.24-0.58; p < 0.001). The cumulative rate of pCR rose up to 83.4% in the 9th week and slowly reached a plateau after the 11th week. Among the patients with pCR, those who received adjuvant chemotherapy had no survival benefits compared to those without adjuvant chemotherapy (adjusted HR: 0.72, 95 CI: 0.27-1.93; p = 0.52). By subgroup analysis, those younger than 70-year old and received adjuvant chemotherapy had better survival benefit than those without adjuvant chemotherapy (adjusted HR: 0.19, 95% CI: 0.04-0.97; p = 0.046). Delayed surgery by 9-12 weeks after the end of neoadjuvant CCRT can maximize the pCR rate, which is correlated with better survival. Adjuvant chemotherapy may be considered in patients with pCR and aged <70-year old, but further prospectively randomized controlled trials are warranted to validate these findings.

Asthma control and severe exacerbations in patients with moderate or severe asthma in Jilin Province, China: a multicenter cross-sectional survey.

BACKGROUND: No systemic evaluation of asthma control in Jilin Province has been reported. Asthma control might provide the basis for asthma management in this region. A multicenter hospital-based cross-sectional study was performed to investigate the asthma control and related factors for severe asthma exacerbations in patients with moderate or severe asthma in Jilin Province, China. METHODS: The study enrolled 1546 patients in five grade one general hospitals from January to December 2013. Asthma medication, patient self-management, asthma control test (ACT) scores and frequency of severe asthma exacerbations during the follow-up (12 months) were collected via a follow-up questionnaire. RESULTS: In the study, 889 patients provided a complete follow-up questionnaire. Severe asthma exacerbations occurred in 54.89 % of patients. ACT score ≤15, asthma medication ≤ 3 months, severe asthma, income level lower than average Per Capita Disposable Income (PCDI) and a lower educational level were risk factors of a severe exacerbation. CONCLUSIONS: Poor adherence to asthma medication, poor asthma symptom control, lower income, a low educational level might be possible reasons for the high incidence of severe asthma exacerbations and poor asthma control in Jilin Province of China.

Synthesis, biological evaluation and molecular modeling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase.

A series of novel 2-aminobenzimidazole derivatives were synthesized under microwave irradiation. Their biological activities were evaluated on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A number of the 2-aminobenzimidazole derivatives showed good inhibitory activities to AChE and BuChE. Among them, compounds 9, 12 and 13 were found to be >25-fold more selective for BuChE than AChE. No evidence of cytotoxicity was observed by MTT assay in PC12 cells or HepG2 cells exposed to 100µM of the compounds. Molecular modeling studies indicate that the benzimidazole moiety of compounds 9, 12 and 13 forms a face-to-face π-π stacking interaction in a 'sandwich' form with the indole ring of Trp82 (4.09Å) in the active gorge, and compounds 12 and 13 form a hydrogen bond with His438 at the catalytic site of BuChE. In addition, compounds 12 and 13 fit well into the hydrophobic pocket formed by Ala328, Trp430 and Tyr332 of BuChE. Our data suggest the 2-aminobenzimidazole drugs as promising new selective inhibitors for AChE and BuChE, potentially useful to treat neurodegenerative diseases.

[Study on mode of delivery and singleton newborns term birth weight in 3 hospitals].

OBJECTIVE: To study newborns weight in singleton term births and the association between newborns birth weight and mode of delivery in 3 hospitals. METHODS: From Jan. 2005 to Dec. 2009, 13 963 singleton term live neonates born in the Department of Obstetrics and Gynecology of Peking University First Hospital (PU group), 6519 neonates in Affiliated Hospital of Binzhou Medical College (BMC group,) and 8725 neonates in Miyun Hospital Affiliated to Capital Medical University, Yanjing Medical College (MYC group) were enrolled in this retrospective study. The newborns weight and the rate of macrosomia was calculated and compared. Those newborns from PU group and MYC group were divided into 2288 neonates at macrosomia group and 20 400 neonates at non-macrosomia group, their mode of deliveries were analyzed. RESULTS: (1) The mean neonatal birth weight were (3386 ± 414) g at PU group, (3389 ± 446) g at BMC group and (3445 ± 449) g at MYC group. Neonates born weight in MYC was significantly higher than those from in PU group and BMC group (P = 0.000). Neonates born weight in BMC showed higher than those in PU group, which did not reached statistical difference (P = 0.638). (2) The incidence of macrosomia were 7.935% (1108/13 963) in PU group, 9.802% (639/6519) in BMU group and 13.524% (1180/8725) in MYU group. The incidence of macrosomia in MYC group was higher than those in PU and BMC group, the incidence of macrosomia in BMC group was higher than that in PU group, which reached statistically difference (P = 0.000). (3)The proportion of cesarean delivery were 75.306% (1723/2288) at macrosomia group, 50.765% (10 356/20 400) at non-macrosomia group, which showed statistical difference (P = 0.000). CONCLUSIONS: (1) The difference of newborns birth weight existed in different administrative level hospital. (2) The risk of cesarean delivery due to macrosomia is higher than that of non-macrosomia. (3) Obstetricians should pay more attention to nutrition in gestation period to lessen the incidence of macrosomia and cesarean section.

Rapid determination of plasma vigabatrin by LC-ESI-MS/MS supporting therapeutic drug monitoring in children with infantile spasms.

Vigabatrin is one of the second-generation anti-seizure medications (ASMs) designated orphan drugs by the FDA for monotherapy for pediatric patients with infantile spasms from 1 month to 2 years of age. Vigabatrin is also indicated as the adjunctive therapy for adults and pediatric patients 10 years of age and older with refractory complex partial seizures. Ideally, the vigabatrin treatment entails achieving complete seizure freedom without significant adverse effects, and the therapeutic drug monitoring (TDM) will make a significant contribution to this aim, which provides a pragmatic approach to such epilepsy care in that the dose tailoring can be undertaken for uncontrollable seizures and in cases of clinical toxicity guided by the drug concentrations. Thus, reliable assays are mandatory for TDM to be valuable, and blood, plasma, or serum are the matrixes of choice. In this study, a simple, rapid, and sensitive LC-ESI-MS/MS method for the measurement of plasma vigabatrin was developed and validated. The sample clean-up was performed by an easy-to-use method, i.e., protein precipitation using acetonitrile (ACN). Chromatographic separation of vigabatrin and vigabatrin-13C,d2 (internal standard) was achieved on the Waters symmetry C18 column (4.6 mm × 50 mm, 3.5 µm) with isocratic elution at a flow rate of 0.35 mL min-1. The target analyte was completely separated by elution with a highly aqueous mobile phase for 5 min, without any endogenous interference. The method showed good linearity over the 0.010-50.0 µg mL-1 concentration range with a correlation coefficient r2 = 0.9982. The intra-batch and inter-batch precision and accuracy, recovery, and stability of the method were all within the acceptable parameters. Moreover, the method was successfully used in pediatric patients treated with vigabatrin and also provided valuable information for clinicians by monitoring plasma vigabatrin levels in our hospital.

Preeclampsia serum upregulates CD40/CD40L expression and induces apoptosis in human umbilical cord endothelial cells.

BACKGROUND: The endothelial cell dysfunction observed in preeclampsia (PE) may be induced by CD40/CD40L signaling. This study investigated the role of CD40/CD40L in the pathogenesis of PE by comparing the effect of maternal serum obtained from healthy pregnant women and PE patients on HUVEC cell growth, apoptosis and CD40/CD40L expression. METHODS: Maternal serum was obtained from 20 patients with PE (PE group) as well as 20 healthy pregnant women (control group). The human umbilical endothelial cell line, CRL1730, was cultured in the presence of maternal serum for 24, 48, and 72 h after which cell growth and apoptosis were assessed by MTT and flow cytometry analysis, respectively. CD40/CD40L expression was determined using flow cytometry and RT-PCR analyses. RESULTS: As compared to CRL1730 cells treated with control sera, those treated with PE sera had altered morphology, decreased cell growth, increased apoptosis and greater CD40/CD40L protein and mRNA expression. Stimulation of CD40/CD40L protein and mRNA expression by PE sera was greatest at 24 h. CONCLUSIONS: PE sera may induce endothelial cell damage possibly through increased CD40/CD40L expression in early-onset PE. Further studies are necessary to determine the factor(s) in PE sera responsible for the observed changes in endothelial cell viability.

Synthesis and bioevaluation of diaryl urea derivatives as potential antitumor agents for the treatment of human colorectal cancer.

The development of inhibitors targeting the PI3K-Akt-mTOR signaling pathway has been greatly hindered by the on-target AEs, such as hyperglycemia and hepatotoxicities. In this study, a series of diaryl urea derivatives has been designed and synthesized based on clinical candidate gedatolisib (6aa), and most of the newly synthesized derivatives showed kinase inhibitory and antiproliferative activities within nanomolar and submicromolar level, respectively. The terminal l-prolineamide substituted derivative 6 ab showed 8.6-fold more potent PI3Kα inhibitory activity (0.7 nM) and 4.6-fold more potent antiproliferative effect against HCT116 cell lines (0.11 µM) compared with control 6aa. The potential antitumor mechanism and efficacy of 6 ab in HCT116 xenograft models have also been evaluated, and found 6 ab showed comparable in vivo antitumor activity with 6aa. The safety investigations revealed that compound 6 ab exhibited more safer profiles in the selectivity of liver cells (selectivity index: >6.6 vs 1.85) and blood glucose regulation than 6aa. In addition, the in vitro stability assays also indicated our developed compound 6 ab possessed good metabolic stabilities.

Long non­coding RNA NEAT1 promotes pulmonary fibrosis by regulating the microRNA­455­3p/SMAD3 axis.

Pulmonary fibrosis is an excessive repair response to tissue damage, triggering hyperplasia of fibrotic connective tissues; however, there is no effective treatment in a clinical setting. The purpose of the present study was to investigate the roles of long non­coding RNA nuclear enriched abundant transcript 1 (NEAT1) and microRNA­455­3p (miR­455­3p) were investigated in pulmonary fibrosis. In this study, the mRNA expression levels of NEAT1, miR­455­3p and SMAD3 in the HPAEpiC alveolar and BEAS­2B bronchial epithelial cell lines were determined using reverse transcription­quantitative PCR, while the markers of epithelial­mesenchymal transformation (EMT) and collagen production were determined using western blot analysis. A wound healing assay was performed to evaluate the migratory ability of the HPAEpiC and BEAS­2B cell lines. The interactions between NEAT1 and miR­455­3p or SMAD3 and miR­455­3p were validated using a luciferase reporter gene assay. The results showed that the mRNA expression levels of NEAT1 and SMAD3 were upregulated in the TGF­ß1­treated HPAEpiC and BEAS­2B cell lines, while the mRNA expression level of miR­455­3p was significantly decreased. In addition, silencing NEAT1 effectively alleviated the migratory ability, EMT and collagen generation of the epithelial cells. Following these experiments, NEAT1 was identified as a sponge for miR­455­3p, and SMAD3 was a target gene of miR­455­3p. NEAT1 downregulation or miR­455­3p mimic inhibited the migratory ability, EMT and collagen production of the epithelial cells; however, the effects were reversed by the overexpression of SMAD3. Furthermore, NEAT1 knockdown reduced the expression level of SMAD3 by increasing the expression level of miR­455­3p to further inhibit the migratory ability, EMT and collagen production of epithelial cells.

Serum Sclerostin But Not DKK-1 Correlated with Central Arterial Stiffness in End Stage Renal Disease Patients.

Sclerostin and dickkopf-1 (DKK1) played a role in the development of cardiovascular diseases and arterial stiffness in chronic kidney disease (CKD) patients but with controversial results of patients in end-stage renal disease (ESRD) including hemodialysis (HD) and peritoneal dialysis (PD). This study aimed to examine the association between the mode of dialysis or the values of sclerostin or DKK1 and carotid-femoral pulse wave velocity (cfPWV) in ESRD patients. There were 122 HD and 72 PD patients enrolled in this study. By a validated tonometry system, cfPWV was measured and then segregated patients into values of >10 m/s as the high central arterial stiffness (AS) group and values ≤ 10 m/s as the control group. Serum levels of sclerostin and DKK1 were measured using a commercial enzyme-linked immunosorbent assay kit. Possible risk factors for the development of AS were analyzed by logistic regression analysis. There were 21 (29.2%) of PD and 53 (43.4%) of HD in the high AS group. Compared to patients in the control group, those in the high AS group were older, had more comorbidities, had higher systolic blood pressure, and had higher serum levels of fasting glucose, C-reactive protein, and sclerostin. Levels of sclerostin (adjusted OR 1.012, 95% CI. 1.006-1.017, p = 0.0001) was found to be an independent predictor of high AS in ESRD patients by multivariate logistic regression analysis. Furthermore, receiver operating characteristic curve analysis showed the optimal cut-off values of sclerostin for predicting AS was 208.64 pmol/L (Area under the curve 0.673, 95% CI: 0.603-0.739, p < 0.001). This study showed that serum levels of sclerostin, but not DKK1 or mode of dialysis, to be a predictor for high central AS in ESRD patients.

Different FDG-PET metabolic patterns of anti-AMPAR and anti-NMDAR encephalitis: Case report and literature review.

INTRODUCTION: 18 F-fluorodeoxyglucose (FDG)-PET metabolic patterns of brain differ among autoimmune encephalitis with different neuronal surface antigens. In this case report, we compared the topographical relationship of cerebral glucose metabolism and antigen distribution in the patients with anti-NMDAR and anti-AMPAR encephalitis. Literature review summarized the common features of brain metabolism of autoimmune encephalitis. METHODS: The cerebral glucose metabolism was evaluated by FDG-PET/CT during acute-to-subacute stage of autoimmune encephalitis and after treatment. The stereo and quantitative analysis of cerebral metabolism used standardized z-score and visualized on three-dimensional stereotactic surface projection. To map NMDAR and AMPAR in human brain, we adopted genetic atlases from the Allen Institute and protein atlases from Zilles's receptor densities. RESULTS: The three-dimensional stereotactic surface projection displayed frontal-dominant hypometabolism in a 66-year-old female patient with anti-AMPAR encephalitis and occipital-dominant hypometabolism in a 29-year-old female patient with anti-NMDAR encephalitis. Receptor density maps revealed opposite frontal-occipital gradients of AMPAR and NMDAR, which reflect reduced metabolism in the correspondent encephalitis. FDG-PET hypometabolic areas possibly represent receptor hypofunction with spatial correspondence to receptor distributions of the autoimmune encephalitis. The reversibility of hypometabolism was in line with patients' cognitive improvement. The literature review summarized six features of metabolic anomalies of autoimmune encephalitis: (a) temporal hypermetabolism, (b) frontal hypermetabolism and (c) occipital hypometabolism in anti-NMDAR encephalitis, (d) hypometabolism in association cortices, (e) sparing of unimodal primary motor cortex, and (e) reversibility in recovery. CONCLUSIONS: The distinct cerebral hypometabolic patterns of autoimmune encephalitis were representative for receptor hypofunction and topographical distribution of antigenic receptors. The reversibility of hypometabolism marked the clinical recovery of autoimmune encephalitis and made FDG-PET of brain a valuable diagnostic tool.

Intestinal Surgery Contributes to Acute Cerebellar Ataxia Through Gut Brain Axis.

Introduction: Acute cerebellar ataxia (ACA) is the most common form of pediatric ataxia. Changes in gut flora can modulate the nervous system, influencing brain function via the gut-brain axis (GBA). This study aimed to illustrate the relationship between intestinal microbiota and ACA. Method: A total of 30 and 12 children were randomly sampled from history of intestinal surgery (HOIS) and no intestinal surgery groups (NHOIS), respectively. In addition, 10 healthy children who sought physical examination in Children's Hospital of Nanjing Medical University were recruited as a control group. The stool samples were 16S rRNA detected. Results: We observed that many ACA children had intestinal surgery history prior to the onset of ACA. The 16S rRNA sequencing indicated that HOIS and control groups were well-distinguished by principal component analysis. The discrepancy between HOIS and NHOIS groups were also displayed by principal component analysis score plot. However, no differences were found between NHOIS and control groups. The results of student's t-test were consistent with principal component analysis. A total of nine different genera were identified between HOIS and control groups. Five genera and a phylum showed significant differences between HOIS and NHOIS groups. Conclusion: Altered genera and phyla associated with ACA were identified. Our findings provide new insight into treating and preventing ACA.

[Three cases of pulmonary alveolar microlithiasis in a family and clinical analysis].

OBJECTIVE: To describe the characteristics of 3 cases of pulmonary alveolar microlithiasis in a family, and therefore to improve the understanding of the disease. METHODS: To analyze the clinical, laboratory and radiological data of three patients with pulmonary alveolar microlithiasis in a family and the relevant literatures were reviewed. RESULTS: There was a typical manifestation in these three cases of pulmonary alveolar microlithiasis: progressive dyspnoea, cough, family history. Chest X-ray and computed tomography demonstrate: the pulmones was full of high density reflection of intra-alveolar microliths especially in middle-lower lobe and posterior lobe. The etiology of these three cases is still unknown, consanguineous marriage of parents is possible reason. There was not effective therapies to them. CONCLUSION: Pulmonary alveolar microlithiasis is a disease without clear known etiology and effective therapy. For a patient with radiological features of high density intra-alveolar microliths and a positive family history, the diagnosis should be highly suspected.

Hypomagnesemia and clinical benefits of anti-EGFR monoclonal antibodies in wild-type KRAS metastatic colorectal cancer: a systematic review and meta-analysis.

Hypomagnesemia is a recognized side-effect of cetuximab- or panitumumab-based chemotherapy for metastatic colorectal cancer (mCRC). The clinical relevance of hypomagnesemia is under debate. Thus, a systematic review and meta-analysis of retrospective studies and randomized clinical trials (RCTs) comparing hypomagnesemia with normal magnesium levels in wild-type KRAS mCRC was performed. One RCT, two retrospective studies, and two American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) conference presentations from phase III RCTs involving 1723 patients were included in this study. Patients with hypomagnesemia demonstrated better progression-free survival (PFS) (Hazard ratio [HR]: 0.64; 95% confidence interval [CI]: 0.47-0.88), overall survival (OS) (HR: 0.72; 95% CI: 0.53-0.92), and objective response rate (ORR) (Risk ratio [RR]: 1.81; 95% confidence interval [CI]: 1.30-2.52). By subgroup analysis, frontline, later lines or combination therapy with hypomagnesemia were associated with PFS benefits (HR: 0.78; 95% CI: 0.62-0.98; HR: 0.60; 95% CI: 0.40-0.90; HR: 0.62; 95% CI: 0.41-0.94, respectively). In patients with wild-type KRAS mCRC, hypomagnesemia is associated with better clinical benefits of PFS, OS and ORR when treated with cetuximab- or panitumumab-based chemotherapy. Future clinical trials should corroborate its predictive role.

Effects of Age and Body Mass Index on Thoracolumbar Spine X-Ray for Diagnosing Osteoporosis in Elderly Women: Tianliao Old People (TOP) Study 07.

PURPOSE: The aim of this study was to determine the effects of diagnostic discordance with or without a thoracolumbar spine lateral view X-ray in patients with osteoporosis. METHODS: We randomly enrolled 368 women over 65 years old (74.3 ± 6.0 years) from Tianliao Township in 2009 (response rate: 75.7%). A diagnosis of osteoporosis was confirmed using one of these criteria: (1) a history of non-traumatic fracture, (2) vertebral fractures based on a thoracolumbar spine lateral view X-ray, or (3) a bone mineral density T-score ≤ -2.5 for the total hip, the femoral neck, the lumbar spine, or all 3 sites. The prevalence of osteoporosis in three groups was compared based on Model I (criteria 1+2) vs. Model II (criteria 1+3) vs. Model III (criteria 1+2+3). The role of thoracolumbar X-ray reflected by the diagnostic discordance of osteoporosis between Models II and III was evaluated. RESULTS: The overall prevalence of osteoporosis was 78.3% (Model III, age-standardized 78.1%). The diagnostic discordance was 17.4% in the 368 participants. A logistic regression model showed that age was negatively associated with diagnostic discordance (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88-0.98, p < 0.05), but body mass index was positively associated (OR = 1.07, 95% CI: 1.00-1.15, p < 0.05). CONCLUSIONS: A thoracolumbar spine lateral view X-ray should be added for women ≥ 65 years old or with a body mass index ≥ 25 kg/m2 to minimize the diagnostic discordance in osteoporosis, especially in highly endemic regions.

Use of the Beers criteria to predict adverse drug reactions among first-visit elderly outpatients.

STUDY OBJECTIVE: To determine whether the Beers criteria can predict adverse drug reactions (ADRs) in first-visit elderly outpatients. DESIGN: Prospective cohort study. SETTING: Outpatient clinics of a tertiary care and academic medical center in southern Taiwan. PATIENTS: Eight hundred eighty-two patients aged 65 years or older who were prescribed drugs at their first visit to either the medical center's outpatient internal medicine clinic or family medicine clinic between March 1, 2001, and July 31, 2001. INTERVENTION: Telephone survey conducted 1 week after clinic visit. MEASUREMENTS AND MAIN RESULTS: Potentially inappropriate drugs were assessed by the updated Beers criteria. Adverse drug reactions were detected by telephone survey and evaluated by the Naranjo criteria 1 week after drug administration. Of the 550 respondents, 64 (11.6%) had potentially inappropriate drugs prescribed and 126 (22.9%) had ADRs. Multiple logistic regression analysis revealed associations between ADRs and potentially inappropriate drug prescribing (relative risk [RR] 15.3, 95% confidence interval [CI] 4.0-58.8), number of prescribed drugs (RR 1.3, 95% CI 1.1-1.5), history of ADRs (RR 2.1, 95% CI 1.3-3.4), and noncompliance with prescribed drugs (RR 2.0, 95% CI 1.1-3.7). In patients who had potentially inappropriate drugs prescribed, the number of prescribed drugs was not significantly associated with ADRs (RR 0.8, 95% CI 0.6-1.1). In patients who did not have potentially inappropriate drugs prescribed, more prescribed drugs increased the risk of ADRs (RR 1.3, 95% CI 1.1-1.5). CONCLUSION: A positive association exists between potentially inappropriate drug prescribing, as defined by the Beers criteria, and ADRs in first-visit elderly outpatients. Clinicians should be alert to the possibility of ADRs if a patient takes more than five drugs, has a history of ADRs, or exhibits poor compliance with prescribed drugs.

Efficacy and safety of bio-chemotherapy with dacarbazine plus interleukin-2 in patients with unresectable malignant melanoma.

AIM: This study retrospectively evaluated the toxicity and efficacy of dacarbazine (DTIC) with low-dose subcutaneous interleukin-2 (IL-2) for patients with advanced melanoma. METHOD: Patients with unresectable malignant melanoma received bio-chemotherapy DTIC (330 mg/m(2) , every 3 weeks ) and IL-2 18 MIU (million international units) in divided doses by subcutaneous injection three times a week for 4 weeks. Treatment was performed for six cycles or until disease progression or unbearable toxicity. RESULTS: From October 2006 to November 2013, up to 31 patients (17 men; 14 women) were enrolled. Their median age was 48 years (range, 22-81 years). Subtypes of melanoma included 11 (35.4%) acral lentiginous, nodular, 1 (3.2%) superficial spreading, 10 (32.2%) mucosal and 5 (16.1%) others. The response rate was 19.3%, including 3.2% with a complete response, 16.1% with a partial response and 6.3% with stable disease. The median progression-free survival time was 3.5 months (95% CI: 3.0-3.9 months). The median overall survival time was 8.6 months (95% CI: 4.1-10.9 months). The 1-year survival rate was 39% and the 5-year survival rate was 10%. CONCLUSIONS: Our data demonstrated that low-dose subcutaneous IL-2 plus DTIC has modest efficacy and may produce long-term survival in small proportion of patients. Furthermore, the treatment is well tolerated by patients.

The Lifespan-Promoting Effect of Otophylloside B in Caenorhabditis elegans.

Aging is the major risk factor for many human diseases and degeneration. Thus, clinically effective medicine could delay the process of aging and aging-related diseases are desperately wanted. In traditional Chinese medicine (TCM), some were claimed to slow down aging. Qingyangshen (Cynanchum otophyllum schneid) is such a TCM. Here, we assayed the longevity effect of compound Otophylloside B (Ot B), a C-21 steroidal glycoside isolated from Qingyangshen, in Caenorhabditis elegans, which is a popular model for aging research. Our results showed that Ot B could modestly extend the lifespan of C. elegans, delay the age-related decline of body movement and improve the stress resistance. Further investigating the molecular mechanism of lifespan extension effect revealed that Ot B could activate the FOXO transcription factor DAF-16. Ot B could not further extend the lifespan of long-lived mutant of insulin/IGF-1-like receptor (daf-2). In addition, Ot B also requires SIR-2.1 and CLK-1 which is an enzyme in ubiquinone synthesis, for lifespan extension.

Potentially inappropriate drug prescribing among first-visit elderly outpatients in Taiwan.

STUDY OBJECTIVE: To determine the prevalence and risk factors of potentially inappropriate drug prescribing among first-visit elderly outpatients. DESIGN: Cross-sectional survey. SETTING: An urban tertiary care and academic medical center in southern Taiwan. PATIENTS: Eight hundred eighty-two patients aged 65 years or older who were prescribed drugs at their first visit to either the medical center's outpatient internal medicine clinic or family medicine clinic between March 1, 2001, and July 31, 2001. MEASUREMENTS AND MAIN RESULTS: Potentially inappropriate drug prescribing was assessed according to updated Beers criteria. Ninety-seven potentially inappropriate drugs were identified in 93 (10.5%) patients. The most common classes were sedative-hypnotics (18.6%) and muscle relaxants (17.5%). Twenty (20.6%) of these inappropriate drugs had a high severity potential according to the Beers criteria. Patients prescribed potentially inappropriate drugs were more likely to be prescribed several drugs versus those who were not prescribed potentially inappropriate drugs (4.0+/-1.9 vs 2.8+/-1.4, p<0.001). Multiple logistic regression analysis revealed an interaction between age and the number of prescribed drugs on the risk of having potentially inappropriate drugs prescribed. In patients who were prescribed four agents or less, the risk was not associated with increasing age; in those who were prescribed five drugs or more, the risk was positively associated with increasing age. CONCLUSION: Potentially inappropriate drug prescribing among first-visit elderly outpatients was relatively low. Increasing patient age combined with increased number of drugs prescribed was associated with increased risk of having potentially inappropriate drugs prescribed.