Associations between Lifestyle Factors and Neurocognitive Impairment among Chinese Adolescent and Young Adult (AYA) Survivors of Sarcoma.

BACKGROUND: The effect of lifestyle on neurocognitive impairment among cancer survivors remain an understudied area. This study explored the association between lifestyle factors and neurocognitive outcomes (specifically, attention, memory, processing speed and cognitive flexibility) in AYA survivors (aged 15-39 years) of sarcoma. METHODS: This study recruited 116 AYA survivors (age 28.2 (SD = 8.2) years), who were diagnosed with osteosarcoma (49%) or soft-tissue sarcoma (51%) at age 13.3 (SD = 7.2) years. The neurocognitive battery included measures of attention, memory, motor-processing speed, and cognitive flexibility. Survivors reported health-damaging practices, which included: physical inactivity, smoking, alcohol intake, inadequate sleep (<7 h of actual sleep/day), sleep-related fatigue (Multidimensional Fatigue Scale) and long working hours (>9 h/day). General linear modeling was conducted to examine the association between lifestyle factors and neurocognitive outcomes, adjusting for age at diagnosis, sex, education attainment and clinical/treatment variables. RESULTS: At 14.9 (SD = 7.6) years post-diagnosis, survivors demonstrated impairment in attentiveness (4.3-13.0%), processing speed (34.5%) and cognitive flexibility (18.1%). Nearly half (45.7%) had developed a chronic health condition (CHC). Low physical activity (estimate = -0.97, p = 0.003) and sleep-related fatigue (estimate = -0.08, p = 0.005) were associated with inattention. Survivors who worked >9 h/day (n = 15) demonstrated worse attention (estimate = 5.42, p = 0.023) and cognitive flexibility (estimate = 5.22, p = 0.005) than survivors who worked ≤9 h/day (n = 66). Interaction analysis (CHCs*physical activity) showed that survivors who developed CHCs and reported low physical activity had worse attention (p = 0.032) and cognitive-flexibility (p = 0.019) scores than other subgroups. CONCLUSION: Treatment-related CHCs, coupled with continued physical inactivity, may exacerbate inattention and executive dysfunction among survivors. Long working hours and sleep-related fatigue are associated with worse functioning; this finding should be validated with prospective assessment of work-related stressors and objective sleep measures.

Analysis of extended thymectomy for the treatment of myasthenia gravis of 527 cases / 中华胸心血管外科杂志

Objective:To summarize the surgical treatment experience of extended thymectomy for myasthenia gravis(MG), and to explore the surgical treatment of MG.Methods:Retrospectively analyzed the clinical data of 527 MG patients undergoing extended thymectomy in our hospital from June 1996 to October 2017, including 242 males and 285 females, aged 5 to 77 years, with a mean age of(52.6±13.7) years old. The course of illness was 12 days to 18 years. There were 22 cases of hyperthyroidism, 7 cases of pure red blood cell aplastic anemia, 1 case each of hypothyroidism, irritable bowel disease, rheumatoid arthritis, ankylosing spondylitis and thrombocytopenia syndrome. There were 272 cases of MG in Osserman Ⅰ, 72 cases inⅡa, 78 cases inⅡb, 81 cases in Ⅲ, and 24 cases in Ⅳ, respectively. The muscle fatigue test and neostigmine test of all patients were positive, and the diagnosis was confirmed by chest CT examination. Meanwhile, summarize the perioperative data and postoperative follow-up.Results:3 cases died during the postoperative period, all of which were thymoma with MG, including 2 cases of Osserman Ⅲ MG and 1 case of Ⅳ MG; 15 cases of postoperative myasthenia crisis, including 2 OssermanⅡb cases, 11 Osserman Ⅲ cases and 2 Osserman Ⅳ cases, also including 7 cases of tracheotomy; 70 cases of plasma exchange, of whom 2 cases of hypotonic syndrome and 2 cases of lower extremity venous thrombosis. The postoperative pathological types were followed by thymic hyperplasia 293 cases(55.60%), thymoma 207 cases(39.28%), thymic cyst 24 cases(4.55%) and thymic atrophy 3 cases(0.57%) in descending order. 378 cases were followed up with an average follow-up of(85.9±58.5)months; MG with complete remission, partial remission, no change and deterioration accounted for 135(35.71%), 192(50.79%), 41(10.85%) and 10(2.65%)cases, respectively. Complete remission rate ranked as Osserman typeⅠ>Ⅱa>Ⅳ>Ⅱb>Ⅲ, the deterioration rate from high to low was Osserman type Ⅲ>Ⅳ>Ⅰ. 18 OssermanⅠcases showed no effects, whose preoperative course of disease> 5-10 years; 1 OssermanⅠcase was worsening who initially was diagnosed with ophthalmic MG and underwent video-assisted thoracoscopic thymectomy. The left thymus lobe was left unresected and developed 6 years later. Another operation was performed to remove the left lobe thymus, confirming the compensatory hypertrophy of the left lobe thymus. Among the worsening patients, 6 died, all of them were thymoma with MG, including 5 cases of type Ⅲ and one case of type Ⅳ. The cause of death was omyasthenia crisis(3 cases), sudden respiratory arrest after 3 months of rapid stopping of brompistigmine(2 cases)and cholinergic crisis(1 case).Conclusion:Standardized extended thymectomy is an effective method for the treatment of MG. Earlier surgery for ocular muscle type MG can effectively reduce the risk of generalization. MG with Osserman Ⅱb or higher is prone to myasthenia crisis. Comprehensive treatments should be taken to reduce MG-related risks. Myasthenia crisis can occur repeatedly in severe patients in the long term after surgery, requiring regular medication and comprehensive MG treatments.

Neurocognitive and Behavioral Outcomes of Chinese Survivors of Childhood Lymphoblastic Leukemia.

BACKGROUND: Increasing attention has been dedicated to investigate modifiable risk factors of late effects in survivors of childhood cancer. This study aims to evaluate neurocognitive and behavioral functioning in a relatively young cohort of survivors of childhood acute lymphoblastic leukemia (ALL) in Hong Kong, and to identify clinical and socio-environmental factors associated with these outcomes. METHODS: This analysis included 152 survivors of childhood ALL who were ≥5 years post-diagnosis (52% male, mean [SD] age 23.5[7.2] years at evaluation, 17.2[7.6] years post-diagnosis). Survivors completed performance-based neurocognitive tests, and reported their emotional and behavioral symptoms using the Child/Adult Behavior Checklist. Socio-environmental variables (living space, fatigue, physical activity, family functioning, and academic stress) were self-reported using validated questionnaires. Clinical variables and chronic health conditions were extracted from medical charts. Multivariable linear modeling was conducted to test identify factors associated with neurocognitive/behavioral outcomes, adjusting for current age, sex, age at diagnosis and cranial radiation. An exploratory mediation analysis was performed to examine the mediating effects of risk factors on neurocognitive and behavioral outcomes. RESULTS: As compared to population norms, a minority of survivors developed mild-moderate impairment in motor processing speed (36.2%), memory (9.2%) and attention measures (4.0%-10.5%). Survivors also reported attention problems (12.5%), sluggish cognitive tempo (23.7%) and internalizing (depressive, anxiety and somatic symptoms) problems (17.1%). A minority of survivors developed mild-moderate treatment-related chronic conditions (n=37, 24.3%). As compared to survivors without chronic conditions, survivors with chronic conditions had more executive dysfunction (B=5.09, standard error [SE]=2.05; P=0.014) and reported more attention problems (B=5.73, SE=1.43; P<0.0001). Fatigue and poor family functioning was associated with multiple measures of behavior problems (all P<0.001). A lower level of physical activity was correlated with more self-reported symptoms of inattention (B= -1.12, SE=0.38, P=0.004) and sluggish cognitive tempo (B=-1.22, SE=0.41, P=0.003). Exploratory analysis showed that chronic health conditions were associated with behavioral measures through fatigue as the mediator. CONCLUSION: The majority of young Chinese survivors of ALL had normal cognitive and behavioral function. Regular monitoring of behavioral function should be performed on survivors who develop treatment-related chronic conditions. Health behavior and socio-environment factors may be potentially modifiable risk factors associated with health outcomes in survivors.

Comparison of Bioavailability and Bioequivalence of Generic and Brand Name Formulations of Escitalopram Oxalate Tablets in Healthy Chinese Population Under Fasting and Fed Conditions.

PURPOSE: This study compared the bioequivalence of two formulations of escitalopram oxalate 20 mg tablets in terms of bioavailability and tolerability in healthy Chinese male and female subjects. PATIENTS AND METHODS: A randomized, single-blind, two-period, two-sequence crossover study was performed under fasting and fed conditions, with a 21-day washout period. In total, 24 healthy subjects (18 males and 6 females) were enrolled in the fasting test and the fed test, respectively. Blood samples were collected over 168 h post-dose in each period. The concentrations of escitalopram in plasma were determined by high-performance liquid chromatography coupled with a tandem mass spectrometry. Pharmacokinetic parameters used for bioequivalence assessment were determined from the drug concentration data using noncompartmental analysis. RESULTS: All subjects showed good medication compliance. The 90% confidence intervals (CIs) for the geometric mean ratios of AUC0-t, AUC0-∞, and Cmax were within the bioequivalence acceptance criteria (80.00% to 125.00%). Adverse events were recorded and no deaths or serious adverse events (SAEs) occurred. CONCLUSION: Escitalopram oxalate 20 mg tablets produced in China were bioequivalent to the reference formulation (Lexapro®) in healthy Chinese male and female subjects under fasting and fed conditions.

Postoperative survival analysis of patients with stage Ⅲ-pN2 non-small cell lung cancer / 中华肿瘤杂志

Objective@#To investigate the effect of mediastinal lymph node resection, metastasis status and treatment on the prognosis of patients with stage Ⅲ-pN2 non-small cell lung cancer (NSCLC).@*Methods@#Clinical data of 206 patients who were pathologically diagnosed as stage Ⅲ-pN2 NSCLC in Tongji Hospital from July 2006 to Dec 2009 were retrospectively analyzed and followed up. Log rank test and Cox proportional hazards regression model were used to analyze the prognostic significance of mediastinal lymph node excision, metastasis state and treatment.@*Results@#The median overall survival (OS) time of the whole group was 29.6 months, and the median disease-free survival (DFS) time was 27.2 months. Univariate analysis showed that the less number of mediastinal lymph node stations with metastasis (single station), the less number of mediastinal lymph nodes involved (less than 2), and postoperative chemotherapy were associated with longer postoperative OS and DFS time (P<0.05 for all). The patients with skip metastasis, negative metastasis of subcarinal lymph node, the lower mediastinal lymph node metastasis rate (MLNR<33%) and postoperative radiotherapy had longer OS and DFS time than those without these factors (P<0.05 for all). Multivariate analysis showed that metastasis of subcarinal lymph node, MLNR and postoperative chemotherapy were the independent prognostic factors for patients with stage Ⅲ-pN2 NSCLC (P<0.05 for all).@*Conclusion@#Metastasis of subcarinal lymph nodes and the higher MLNR might shorten the postoperative survival time of NSCLC patients with stage Ⅲ-pN2, whereas postoperative chemotherapy prolongs the survival time.

Three novel structural phenomena in the cellular ontogeny of Oenococcus oeni from northern China.

Stress resistance and growth are important aspects to consider when engineering Oenococcus oeni strains for winemaking. We identified 3 previously unreported structural phenomena in the cell ontogeny of O. oeni sampled in northern China. We show that budding and binary fission (BBF) occur simultaneously in the growth process; that a novel 'pomegranate-shaped structure' (PSS) occurs mainly in the stationary and death phases; and that symbiosis and cyclical phenomena (SCP) occur throughout the various cell growth phases. These observations add to the current knowledge of the cell growth process of O. oeni. BBF, PSS, and SCP sufficiently describe the characteristics of the cellular ontogeny of O. oeni. We highlight a newly identified structure that explains the complex cell growth process. These findings will help understand the growth and development of O. oeni, supplementing the knowledge base of the established phases and providing new perspectives into its complex growth patterns.

Quantification of Niacin and Its Metabolite Nicotinuric Acid in Human Plasma by LC-MS/MS: Application to a Clinical Trial of a Fixed Dose Combination Tablet of Niacin Extended-Release/Simvastatin (500 mg/10 mg) in Healthy Chinese Volunteers.

Our paper aimed to develop rapid, sensitive, and specific LC-MS/MS method for the quantification of niacin (NA) and its metabolite nicotinuric acid (NUA) in human plasma. Following protein precipitation with acetonitrile, the NA, NUA, and internal standard (5-fluorouracil) were separated on a Zorbax 300SB-C8 column (250 mm × 4.6 mm, 5 µm) with a mobile phase consisting of methanol-2 mM ammonium acetate (3 : 97, v/v) at a flow rate of 1 mL/min (split 1 : 1). A tandem mass spectrometer equipped with electrospray ionization source was used as the detector and operated in negative ion mode. The linear concentration ranges of the calibration curves were 5-800 ng/mL for NA and NUA. The intra-assay RSD for quality control (QC) samples were from 5.0% to 8.7% for NA, and 5.5% to 7.6% for NUA. The interassay RSD for QC samples were from 2.8% to 9.4% for NA, and 3.7% to 5.8% for NUA. The relative errors for QC samples were from -2.2% to 2.3% for NA, and -0.6% to 3.2% for NUA. The method was successfully applied to the investigation of the pharmacokinetic profiles of NA, NUA in human after single dose administration of Niacin extended-release/Simvastatin tablet (500 mg/10 mg).

The application of an LC-MS/MS method in a pharmacokinetic study for the determination of the concentration of nifekalant in human plasma.

In the present study, a simple, rapid, and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of the concentration of Nifekalant in human plasma was developed and validated. The analyte and the internal standard were extracted from human plasma using dichloromethane and analyzed using an ultra-fast liquid chromatographer (UFLC) coupled to an electrospray ionization (ESI) tandem mass spectrometer in the positive mode. The chromatographic analysis was performed isocratically on an Inertsil ODS-SP column (150mm×4.6mm I.D., 5µm). The mobile phase was a mixture of 15% 10mM aqueous ammonium formate and 85% methanol (the pH was adjusted to 3.5 with formic acid) at a flow rate of 0.8mL/min with a split ratio of 1:1 to the ionization source. The lower limit of quantification (LLOQ) was 5.05ng/mL, and a linear calibration curve was obtained over the concentration range of 5.05 to 3030ng/mL. The intra-day and inter-day assay variations were less than 9.06%, and the accuracy values (relative error) were in the range of -10.95% to 2.27%. The essential pharmacokinetic parameters of the intravenously injection of Nifekalant were found to be the following: t1/2=1.26±0.16h,Cmax=1.943±0.411mg/L, and AUC0-12h=4.600±0.756mg/L·h.

Inhibitory control differentiates rare target search performance in children.

Age-related differences in rare-target search are primarily explained by the speed-accuracy trade-off, primed responses, or decision making. The goal was to examine how motor inhibition influences visual search. Children pressed a key when a rare target was detected. On no-target trials, children withheld reactions. Response time (RT), hits, misses, correct rejection, and false alarms were measured. Tapping tests assessed motor control. Older children tapped faster, were more sensitive to rare targets (higher d'), and reacted more slowly than younger ones. Girls outperformed boys in search sensitivity but not in RT. Motor speed was closely associated with hit rate and RT. Results suggest that development of inhibitory control plays a key role in visual detection. The potential implications for cognitive-motor development and individual differences are discussed.

Determination of ethambutol hydrochloride in the combination tablets by precolumn derivatization.

A new high-performance liquid chromatography method for the quantitative determination of ethambutol hydrochloride in combination tablets is presented. Ethambutol is derivatized with phenylethylisocyanatate at room temperature (22 +/- 2 degrees C) for 5 min. Separation is performed by a C(18) column using methanol-water-glacial acetic acid (70:30:0.2, v/v/v) as the mobile phase. The method is linear for drug concentrations in the range of 20-120 microg/mL (r=0.9995). The intra- and inter-day precisions are lower than 1.46% and 2.22%, respectively. The average recovery of the samples at three levels is 99.8%. The results show that derivatization of ethambutol is stable at 30 degrees C for 24 h. This method is simple, rapid, and stable in the presence of common excipients and antituberculosis drugs in the tablets.

[Determination of adenosine, rutin and quercetin in Carthamus tinctorius by HPCE].

AIM: To develop a method for determination of adenosine, rutin and quercetin in Carthamus tinctorius L. by high performance capillary electrophoresis(HPCE). METHODS: A fused silica capillary (66.5 cm x 50 microns ID, an effective length of 58 cm) was used. The running buffer composed of 50 mmol.L-1 borax (pH 9.7) containing 18% methanol. The applied voltage was 24 kV and the capillary temperature was 20 degrees C. The detection wavelength was 210 nm. Rifampicin was used as internal standard. RESULTS: A good linearity between peak area ratio of the common peak to the internal standard and the concentration was found in the range of 10-160 mg.L-1 for adenosine, 100-2,000 mg.L-1 for rutin and 100-1,600 mg.L-1 for quercetin (r > 0.998). The average recoveries were 98.5%-100.5%, 96.9%-99.5% and 99.1%-99.5% for adenosine, rutin and quercetin, respectively. The relative standard deviation was less than 6.5% (n = 5). CONCLUSION: The method is simple, rapid and with satisfactory recoveries and good reproducibilities. It can be used to control the quality of Carthamus tinctorius.

Fingerprint analysis of Flos Carthami by capillary electrophoresis.

Capillary electrophoresis (CE) was employed in fingerprint analysis of Flos Carthami. A standardized procedure was used to develop the CE fingerprint. An electrophoretic profile of genuine Flos Carthami from Fengqiu, He'nan, China, was first established as the characteristic fingerprint. This profile was then used to identify and assess the consistency of the herb. A study with a limited number of samples from nine sources showed a fair consistency in their CE fingerprints with that of the genuine sample. Flos Carthami was well distinguished from Stigma Croci, a possible substitute in traditional Chinese medicine, and Flos Hemerocallis, a commercial adulterant, by comparing the fingerprints of each herb.

Determination of ferulic acid and adenosine in Angelicae Radix by micellar electrokinetic chromatography.

A micellar electrokinetic chromatography for determining ferulic acid and adenosine in Angelicae Radix was developed. A buffer solution composed of 50 mmol L(-1) borax, 10 mmol L(-1) sodium deoxycholate, and 2% methanol was found to be the most suitable electrolyte for the separation. The contents of ferulic acid and adenosine in Angelicae Radix were determined within 20 min. Good linearity between peak area ratio and the concentration was found in the range of approximately 20-320 microg mL(-1) for ferulic acid and about 10-160 microg mL(-1) for adenosine ( r >0.998), respectively. The recoveries were approximately 96.8-97.4% and 93.2-95.0%, and the RSD of this proposed method were 4.4% and 3.2% for ferulic acid and adenosine, respectively ( n=5). The contents of ferulic acid and adenosine in Angelicae Radix from different sources were determined.

[Studies on diclofenac sodium pulsatile release pellets].

AIM: To investigate the preparation of diclofenac sodium pulsatile release pellets (DS-PRP), the release in vitro and the pharmacokinetics of the drug. METHODS: Diclofenac sodium (DS) core pellets prepared by extrusion-spheronization technology were coated in a mini-fluidized bed spray coater with swelling material as the inner coating swelling layer and ethylcellulose aqueous dispersion as the outer coating controlled layer. The effects of formulation and medium on pulsatile release of DS were investigated under release rate test. Pharmacokinetic and bioavailability study in eight human subjects were performed by HPLC method. RESULTS: The delayed-release time and release rate of DS from DS-PRP were influenced obviously by the swelling material, the concentration of SDS in medium, the coating level of the inner swelling layer and the outer controlled layer. In vitro, the delayed-release time T0.1 was 3.1 h, and the pulsed-release time T0.1-0.2 was 1.2 h. In vivo, the delayed-release time Tlag was 2.8 h, and the bioavailability was (91 +/- 12)%. CONCLUSION: The release of drug from DS-PRP was shown to be in pulsed way both in vitro and in vivo.