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.

Nomogram Based on US and Clinicopathologic Characteristics: Axillary Nodal Evaluation Following Neoadjuvant Chemotherapy in Patients With Node-Positive Breast Cancer.

BACKGROUND: To develop a convenient modality to predict axillary response to neoadjuvant chemotherapy (NAC) in breast cancer patients. MATERIALS AND METHODS: In this multi-center study, a total of 1019 breast cancer patients with biopsy-proven positive lymph node (LN) receiving NAC were randomly assigned to the training and validation groups at a ratio of 7:3. Clinicopathologic and ultrasound (US) characteristics of both primary tumors and LNs were used to develop corresponding prediction models, and a nomogram integrating clinicopathologic and US predictors was generated to predict the axillary response to NAC. RESULTS: Axillary pathological complete response (pCR) was achieved in 47.79% of the patients. The expression of estrogen receptor, human epidermal growth factor receptor -2, Ki-67 score, and clinical nodal stage were independent predictors for nodal response to NAC. Location and radiological response of primary tumors, cortical thickness and shape of LNs on US were also significantly associated with nodal pCR. In the validation cohort, the discrimination of US model (area under the curve [AUC], 0.76) was superior to clinicopathologic model (AUC, 0.68); the combined model (AUC, 0.85) demonstrates strong discriminatory power in predicting nodal pCR. Calibration curves of the nomogram based on the combined model demonstrated that substantial agreement can be observed between the predictions and observations. This nomogram showed a false-negative rates of 16.67% in all patients and 10.53% in patients with triple negative breast cancer. CONCLUSION: Nomogram incorporating routine clinicopathologic and US characteristics can predict nodal pCR and represents a tool to aid in treatment decisions for the axilla after NAC in breast cancer patients.

Efficacy of Children Neuropsychological and Behavioral Scale in Screening for Autism Spectrum Disorders through a Combination of Developmental Surveillance.

OBJECTIVE: This study aimed to explore the clinical value of Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) for Autism Spectrum Disorder (ASD) screening in the presence of developmental surveillance. METHODS: All participants were evaluated by the CNBS-R2016 and Gesell Developmental Schedules (GDS). Spearman's correlation coefficients and Kappa values were obtained. Taking GDS as a reference assessment, the performance of the CNBS-R2016 for detecting the developmental delays of children with ASD was analyzed with receiver operating characteristic (ROC) curves. The efficacy of the CNBS-R2016 to screen for ASD was explored by comparing Communication Warning Behavior with Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). RESULTS: In total, 150 children aged 12-42 months with ASD were enrolled. The developmental quotients of the CNBS-R2016 were correlated with those of the GDS (r=0.62-0.94). The CNBS-R2016 and GDS had good diagnostic agreement for developmental delays (Kappa=0.73-0.89), except for Fine Motor. There was a significant difference between the proportions of Fine Motor, delays detected by the CNBS-R2016 and GDS (86.0% vs. 77.3%). With GDS as a standard, the areas under the ROC curves of the CNBS-R2016 were above 0.95 for all the domains except Fine Motor, which was 0.70. In addition, the positive rate of ASD was 100.0% and 93.5% when the cut-off points of 7 and 12 in the Communication Warning Behavior subscale were used, respectively. CONCLUSION: The CNBS-R2016 performed well in developmental assessment and screening for children with ASD, especially by Communication Warning Behaviors subscale. Therefore, the CNBS-R2016 is worthy of clinical application in children with ASD in China.

The Value of Contrast-Enhanced Ultrasound in the Detection of Sentinel Lymph Nodes in Malignant Melanoma.

OBJECTIVE: To evaluate the location and characterization value of contrast-enhanced ultrasound (CEUS) in the detection of sentinel lymph nodes (SLNs) in malignant melanoma. METHODS: SLNs and the lymph node network were tracked by subcutaneous injection of ultrasonic contrast agent around the tumor and preoperative localization, and qualitative analyses were performed. The SLNs were also detected by the intraoperative subcutaneous injection of carbon nanoparticles, and the findings were compared with lymph nodes located by CEUS. The accuracy of the preoperative lymph node identification was evaluated by the results of postoperative pathology, which served as the gold standard of detection. RESULTS: In 47 patients with malignant melanoma, the mean number of SLNs detected by CEUS was 1.72 ± 0.10, while that by carbon nanoparticle administration it was 1.79 ± 1.07 (P = .371 > .05). Seven cases of lymph node metastasis were detected by CEUS, with a sensitivity of 70.0%, specificity of 97.3%, positive predictive value of 87.5%, negative predictive value of 92.3%, and accuracy of 91.5%. There was high consistency between the findings of CEUS and pathology in differentiating benign and malignant lymph nodes (kappa = 0.726, χ2  = 25.243, P < .001). CONCLUSIONS: CEUS can localize and differentiate SLNs in malignant melanoma, and thus, may potentially guide clinical treatment in the future.

Safety of inactivated COVID-19 vaccine in tuberous sclerosis complex patients with epilepsy treated with rapamycin.

PURPOSE: To assess the safety of inactivated coronavirus 2019 disease (COVID-19) vaccine in tuberous sclerosis complex (TSC) patients with epilepsy. METHODS: All patients with epilepsy were selected from Efficacy and Safety of Sirolimus in Pediatric Patients with Tuberous Sclerosis (ESOSPIT) project and younger than 17 years old. The patients were treated with mTOR inhibitors (rapamycin). A total of 44 patients who completed the two-dose inactivated COVID-19 vaccine between July 7, 2021, and January 1, 2022, were enrolled. RESULTS: The median age of seizure onset was 23 months. About two-thirds of patients have focal seizures. Thirty-three patients use antiseizure medications. The mean duration of rapamycin treatment was 55.59 ± 18.42 months. Adverse reactions within 28 days after injection occurred in 11 patients (25%), all were under 12 years old. Injection site pain was the most reported event (20.45%), which was mild in severity and improved within one day. All patients had no seizure-related changes after vaccination. CONCLUSION: This study shows that the inactivated COVID-19 vaccine was well tolerated and safe in TSC patients with epilepsy, as well as for those treated with mTOR inhibitors.

Efficacy of IOTA simple rules, O-RADS, and CA125 to distinguish benign and malignant adnexal masses.

OBJECTIVE: Ovarian cancer is the most deadly deadliest gynecological tumor in the female reproductive system. Therefore, the present study sought to determine the diagnostic performance of International Ovarian Tumor Analysis Simple Rules (IOTA SR), the Ovarian-Adnexal Reporting and Data System (O-RADS), and Cancer Antigen 125 (CA125) in discriminating benign and malignant ovarian tumors. The study also assessed whether a combination of the two ultrasound categories systems and CA125 can improve the diagnostic performance. METHODS: A total of 453 patients diagnosed with ovarian tumors were retrospectively enrolled from Fujian Cancer Hospital between January 2017 and September 2020. The data collected from patients included age, maximum lesion diameter, location, histopathology, levels of CA125, and detailed ultrasound reports. Additionally, all ultrasound images were independently assessed by two ultrasound physicians with more than 5 years of experience in the field, according to the IOTA simple rules and O-RADS guidelines. Furthermore, the area under the curve (AUC), sensitivity, and specificity of the above mentioned predictors were calculated using the receiver operating characteristic curve. RESULTS: Out of the 453 patients, 184 had benign lesions, while 269 had malignant ovarian tumors. In addition, the AUCs of IOTA SR, O-RADS, and CA125 in the overall population were 0.831, 0.804, and 0.812, respectively, and the sensitivities of IOTA SR, O-RADS, and CA125 were 94.42, 94.42, and 80.30%, respectively. On the other hand, the AUCs of IOTA SR combined with CA125, O-RADS combined with CA125, and IOTA SR plus O-RADS combined with CA125 were 0.900, 0.891, and 0.909, respectively. The findings also showed that the AUCs of a combination of the three approaches were significantly higher than those of individual strategies (p<0.05) but not significantly higher than the AUC of a combination of two methods (p>0.05). CONCLUSION: The findings showed that a combination of IOTA SR or O-RADS in combination with CA125 may improve the ability to distinguish benign from malignant ovarian tumors.

Short-term efficacy of superficial X-ray treatment for infantile maxillofacial hemangioma.

OBJECTIVES: This study aimed to explore the short-term clinical efficacy and factors influencing low-dose superficial X-ray for treating infantile maxillofacial hemangioma. METHODS: Retrospective analysis was conducted on 161 cases of infants with maxillofacial hemangioma treated with superficial X-ray in the Laser Center of Dermatology Department of Sichuan Provincial People's Hospital from January 2015 to December 2017. Clinical efficacy was analyzed by comparing the photos before and after treatment. Patients were further divided into groups according to different genders, age at the start of treatment, preterm birth or low birth weight, hemangioma site, longest diameter of hemangioma, and type of hemangioma to analyze whether differences existed in clinical efficacy and therapeutic dose between different groups. RESULTS: Twelve months after the end of treatment, the overall cure rate was 93.8%, and the significant efficiency was 97.5%. The clinical efficacy was related to the age of children at the beginning of treatment and the type of hemangioma (P<0.05). The clinical efficacy of children aged less than or equal to 12 months and superficial hemangioma group was better than that of children aged more than 12 months and deep subtype or mixed hemangioma group, respectively. Therapeutic doses associa-ted with hemangioma treatment with diameter, category, age (P<0.05), diameter greater than or equal to 4 cm hemangioma group, the mixed type or deep in the group, the children older than 12 months hemangioma group, respectively, the dia-meter is less than 4 cm hemangioma, superficial hemangioma group and age less than or equal to 12 months hemangioma total treatment group exposure dose is greater. CONCLUSIONS: Low-dose superficial X-ray is safe and effective for the treatment of infantile maxillofacial hemangioma. Age and type of hemangioma at the time of treatment are the factors influencing therapeutic dose and clinical efficacy.

Activating molecular oxygen with Au/CeO2 for the conversion of lignin model compounds and organosolv lignin.

Au/CeO2 was demonstrated to be a high efficiency catalyst for the conversion of 2-phenoxyacetophenol (PP-ol) employing O2 as an oxidant and methyl alcohol as the solvent without using an erosive strong base or acid. Mechanistic investigations, including emission quenching experiments, electron spin-resonance (ESR) and intermediate verification experiments, were carried out. The results verified that the superoxide anion activated by Au/CeO2 from molecular oxygen plays a vital role in the oxidation of lignin model compounds, and the cleavage of both the ß-O-4 and Cα-Cß linkages was involved. Au/CeO2 also performed well in the oxidative conversion of organosolv lignin under mild conditions (453 K), producing vanillin (10.5 wt%), methyl vanillate (6.8 wt%), methylene syringate (3.4 wt%) and a ring-opened product. Based on the detailed characterization data and mechanistic results, Au/CeO2 was confirmed to be a promising catalytic system.

Guidelines and recommendations on the clinical use of shear wave elastography for evaluating thyroid nodule1.

Ultrasound elastography has been introduced into clinical practice for a decade and arisen continuous increasing attention worldwide. Shear wave elastography (SWE) is a further extension of ultrasound elastography on the basis of strain elastography, providing a two-dimensional distribution map of tissue stiffness and quantitative measurement of the tissue stiffness in Young's modulus (kPa) and/or shear wave speed (m/s). The Society of Ultrasound in Medicine, Chinese Medical Association (CMA) has recently released a series of guidelines for the use of SWE, including the technique and principle of SWE, and use of SWE in liver fibrosis, breast, thyroid, and musculoskeletal system. Herein, a part of SWE in thyroid nodules is presented. In this guideline, the background, classification and technology of SWE, examination methods, diagnostic performance, prognosis evaluation, reproducibility, and limitations are discussed and recommendations are given. The recommendations are based on the published literatures with regard to SWE with different levels of evidence, particularly a mid-term result of the prospective multi-center clinical trial of SWE in thyroid, as well as the Society of Ultrasound in Medicine, CMA expert's consensus. The document provides an overall analysis of SWE in thyroid from clinical perspective, which aimed to provide recommendations to the clinicians with regard to the management of thyroid nodules by the assistance of SWE.

Monitoring of pH changes in a live rat brain with MoS2/PAN functionalized microneedles.

Monitoring the dynamic pH changes in vivo remains very essential to comprehend the function of pH in various physiological processes. In this study, we report a high-performance electrochemical pH microneedle based on an acupuncture needle (AN) for real-time monitoring of pH changes in a rat brain. The pH microneedle was prepared by a layer-to-layer assembly of molybdenum disulfide (MoS2) nanosheets and polyaniline (PAN), with an attempt to achieve a highly sensitive detection of hydrogen ions (H+). The as-prepared PAN/MoS2/AN exhibited a high Nernstian response of -51.2 mV per pH over a wide pH range from 3.0 to 9.0, and excellent selectivity toward pH against other potential interfering species in the brain. Moreover, the corresponding open circuit potential rapidly increased and decreased when Na2CO3 or NaH2PO4 was injected into the rat brain, respectively, demonstrating that the PAN/MoS2/AN has an excellent response toward pH changes in vivo. This work provides a new potentiometric method for real-time monitoring of dynamic pH changes in vivo with high reliability and stability.

A Proposal to Stratify the Intermediate-Risk Thyroid Nodules According to the AACE/ACE/AME Guidelines with Ultrasound Features.

To propose a risk stratification system for intermediate-risk thyroid nodules (TNs) according to American Association of Clinical Endocrinologists, American College of Endocrinology and Associazione Medici Endocrinologi Medical (AACE/ACE/AME) Guideline with ultrasound (US) features. 1000 patients with 1000 nodules (902 benign nodules and 98 malignant nodules) were included. All the nodules were confirmed with either fine needle aspiration (FNA) cytology and follow-up or histology results after surgery. Univariate analysis and binary multivariate logic regression analysis were applied to analyze the possible risk US features associated with malignancy. Receiver operating characteristic curves (ROC) were drew and compared. Univariate analysis and binary multivariate logistic regression analysis showed that indeterminate hyper-echoic spot (OR = 4.544), slightly ill-defined margin (OR = 2.559), slight hyper-echogenicity (OR = 1.992) and no macro-calcification (OR = 1.921) were risk factors for the intermediate-risk thyroid nodules (TNs). A predicting model was established based on the 4 risk factors. The risk rates of malignancy were 5.7% (26/455) in Stage I, 11.0% (49/445) in Stage II, 23.1% (21/91) in Stage III, 33.3% (3/9) in Stage IV. In conclusion, for the intermediate-risk TNs, special attention should be paid to the TNs with indeterminate hyper-echoic spot, slightly ill-defined margin, slight hyper-echogenicity, or no macro-calcification. The probability of malignancy increased with the number of risk factors increasing.

MoS2/Pt nanocomposite-functionalized microneedle for real-time monitoring of hydrogen peroxide release from living cells.

This work describes the adaptive use of a conventional stainless steel acupuncture needle as the electrode substrate for construction of a molybdenum disulfide (MoS2) and platinum nanoparticles (PtNPs) layer-modified microneedle sensor for real-time monitoring of hydrogen peroxide (H2O2) release from living cells. To construct the nanocomposite-functionalized microneedle, the needle surface was first coated with a gold film by ion sputtering to enhance the conductivity. Subsequently, an electrochemical deposition method was successfully employed to deposit MoS2 nanosheet and Pt nanoparticles on the needle tip as the sensing interface. Electrochemical study demonstrated that the MoS2/PtNPs nanocomposite-modified needle exhibited excellent catalytic performance and low over-potential toward the reduction of H2O2. Not only did the microneedle achieve a wide linear range from 1 to 100 µmol L-1 with a limit of detection down to 0.686 µmol L-1, but it also realized the highly specific detection of H2O2. Owing to these remarkable analytical advantages, the prepared microneedle was applied to determine H2O2 release from living cells with satisfactory results. The MoS2/PtNPs nanocomposite-functionalized microneedle sensor is simple and affordable, and can serve as a promising electrochemical nonenzymatic sensing platform. Moreover, this superfine needle sensor shows great potential for real-time monitoring of reactive oxygen species in vivo with minimal damage.

Factors associated with trait anger level of juvenile offenders in Hubei province: A binary logistic regression analysis.

The risk factors of high trait anger of juvenile offenders were explored through questionnaire study in a youth correctional facility of Hubei province, China. A total of 1090 juvenile offenders in Hubei province were investigated by self-compiled social-demographic questionnaire, Childhood Trauma Questionnaire (CTQ), and State-Trait Anger Expression Inventory-II (STAXI-II). The risk factors were analyzed by chi-square tests, correlation analysis, and binary logistic regression analysis with SPSS 19.0. A total of 1082 copies of valid questionnaires were collected. High trait anger group (n=316) was defined as those who scored in the upper 27th percentile of STAXI-II trait anger scale (TAS), and the rest were defined as low trait anger group (n=766). The risk factors associated with high level of trait anger included: childhood emotional abuse, childhood sexual abuse, step family, frequent drug abuse, and frequent internet using (P<0.05 or P<0.01). Birth sequence, number of sibling, ranking in the family, identity of the main care-taker, the education level of care-taker, educational style of care-taker, family income, relationship between parents, social atmosphere of local area, frequent drinking, and frequent smoking did not predict to high level of trait anger (P>0.05). It was suggested that traumatic experience in childhood and unhealthy life style may significantly increase the level of trait anger in adulthood. The risk factors of high trait anger and their effects should be taken into consideration seriously.

Factors Associated with Trait Anger Level of Juvenile Offenders in Hubei Province: A Binary Logistic Regression Analysis / 华中科技大学学报（医学）（英德文版）

The risk factors of high trait anger of juvenile offenders were explored through question naire study in a youth correctional facility of Hubei province,China.A total of 1090 juvenile offenders in Hubei province were investigated by self-compiled social-demographic questionnaire,Childhood Trauma Questionnaire (CTQ),and State-Trait Anger Expression Inventory-Ⅱ (STAXI-Ⅱ).The risk factors were analyzed by chi-square tests,correlation analysis,and binary logistic regression analysis with SPSS 19.0.A total of 1082 copies of valid questionnaires were collected.High trait anger group (n=316) was defined as those who scored in the upper 27th percentile of STAXI-Ⅱ trait anger scale (TAS),and the rest were defined as low trait anger group (n=766).The risk factors associated with high level of trait anger included:childhood emotional abuse,childhood sexual abuse,step family,frequent drug abuse,and frequent internet using (P＜0.05 or P＜0.01).Birth sequence,number of sibling,ranking in the family,identity of the main care-taker,the education level of care-taker,educational style of care-taker,family income,relationship between parents,social atmosphere of local area,frequent drinking,and frequent smoking did not predict to high level of trait anger (P＞0.05).It was suggested that traumatic experience in childhood and unhealthy life style may significantly increase the level of trait anger in adulthood.The risk factors of high trait anger and their effects should be taken into consideration seriously.

In vivo Monitoring of Serotonin by Nanomaterial Functionalized Acupuncture Needle.

Acupuncture treatment is amazing but controversial. Up to now, the mechanism of treating diseases by acupuncture and moxibustion is still unclear, especially the occurrence of the molecular events in local acupoints. Herein, we report an extremely stable microsensor by modifying carbon nanotube (CNT) to the tip surface of acupuncture needle and applying this CNT-modified acupuncture needle for real time monitoring of serotonin (5-HT) in vivo. To stabilize CNT modification on the needle tip surface, poly(3,4-ethylenedioxythiophene)(PEDOT) was employed as glue water to stick CNT on the needle. The detection limit of the CNT-modified needle was found to be approximately 50 nM and 78 nM in the PBS and the cell medium, respectively. In addition, the needle showed good selectivity to some inflammatory mediators and some electroactive molecules. For the first time, the CNT-modified needle could be directly probed into rat body for real time monitoring of 5-HT in vivo, showing a great potential for better understanding the mechanism of acupuncture treatment.

[Diagnostic value of Kimura's disease with ultrasonography].

OBJECTIVE: To explore the diagnostic value of ultrasonography for Kimura's disease (KD). METHODS: Retrospectively analyzed the results of two dimension and color Doppler of 21 Kimura's disease carried by 19 patients who were resected and confirmed by pathologhy. RESULTS: Twenty-one KD cases were detected by the ultrasound while none of them was diagnosed by ultrasonography. 21 cases were showed in the lymph nodes (42.9%, 9/21), parotid gland (4.8%, 1/21) and soft tissues (52.4%, 11/21). The masses both in the lymph and in the parotid gland marked hypoechogenicity and round or like-round. Cases in the soft tissues marked hypoechogencity or hyperechogenicity. Color Doppler flow pattern II to III were showed in 19 cases (90.5%, 19/21). CONCLUSION: Ultrasonography enables a confident preoperative diagnosis of Kimura's disease.

Comparison of pemetrexed plus cisplatin with gemcitabine plus docetaxel in refractory/metastatic osteosarcoma: Clinical outcomes from a retrospective database monitored in a single institute.

The prognosis for patients with relapsed/metastatic osteosarcoma is poor and the optimal treatment strategy remains to be refined. Whilst gemcitabine plus docetaxel combination treatment has already been demonstrated to have certain promising results in the treatment of osteosarcoma, the use of pemetrexed, a multi-targeted antifolate, remains controversial. In the present study, a retrospective investigation was conducted to evaluate the toxicity and efficacy of the pemetrexed plus cisplatin combination in relapsed/metastatic osteosarcoma. Comparison of this treatment with that of the gemcitabine plus docetaxel combination was also conducted. Clinical data from 39 patients suffering from refractory/metastatic osteosarcoma between January 2005 and May 2011 were reviewed retrospectively. Of these patients, 21 were administered the gemcitabine plus docetaxel combination, and 18 were provided the pemetrexed plus cisplatin combination. Treatment was continued until the occurrence of disease progression or unacceptable toxicity. In the gemcitabine plus docetaxel group, the overall response rate and disease control rate were found to be 9.5 and 28.5% respectively, compared with 5.5 and 33.3% respectively in the pemetrexed plus cisplatin group. The median progression-free survival (PFS) time was found to be 1.8 months for both the gemcitabine plus docetaxel and pemetrexed plus cisplatin groups. The median overall survival (OS) time was 6 months in the gemcitabine plus docetaxel group and 7 months in the pemetrexed plus cisplatin group. No statistically significant differences were recognized between the overall response rates, disease control rates, PFS times and OS times in the two groups. The two combinations appeared to be well tolerated. However, the incidence of grade 3/4 thrombocytopenia and leucopenia was higher in the gemcitabine plus docetaxel group than in the pemetrexed plus cisplatin group. The present study clearly demonstrated that both chemo-combinations were well-tolerated and exerted antitumor activity in patients with refractory/metastatic osteosarcoma. However, with regard to grade 3/4 toxicity, the pemetrexed plus cisplatin chemotherapy appears to be better tolerated.

[Evaluation of the sedative and hypnotic effects of H1208].

This study is to investigate the sedative and hypnotic effects of a novel compound H1208. The sedative activity of H1208 was investigated by recording the spontaneous locomotor activity of mice. The hypnotic property was evaluated by the latency and duration of sleep (loss of righting reflex) in mice and the effect of hypnotics on sleep pattern of electroencephalogram were studied in conscious, freely moving mice with chronically implanted electrodes. The brain monoamine neurotransmitters levels in mice were measured by high performance liquid chromatography-electrochemical detection. The spontaneous locomotor activity was decreased by 56.7% and 80.2% in H1208 (5 and 25 mg x kg(-1), ip) treated mice, respectively. The loss of righting reflex was directly induced in mice after H1208 (60 mg x kg(-1), ip) administration. The non-rapid eye movement sleep increased significantly by 131% and 259%, respectively, within 3 hours after H1208 (30 and 60 mg x kg(-1), ip) administration. However, the rapid eye movement sleep decreased significantly. The contents of DA in the striatum and cortex and 5-HT in the cortex decreased significantly. These results demonstrated that H1208 has potent sedative and hypnotic effects, which may be closely related to the decreased contents of DA and 5-HT in mouse brain.

Risk of arterial thromboembolic events with vascular endothelial growth factor receptor tyrosine kinase inhibitors: an up-to-date meta-analysis.

PURPOSE: Arterial thromboembolic events (ATEs) with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) have emerged as a serious concern, we perform a meta-analysis of randomized controlled trials (RCTs) to determine the incidence and risk of ATEs in cancer patients treated with these agents. METHODS: The databases of PubMed and Web of Science were searched for relevant articles. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR), and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies. RESULTS: A total of 9711 patients from 19 RCTs were included. The overall incidence of ATEs was 1.5% (95%CI: 1.0-2.3%). The use of VEGFR-TKIs significantly increased the risk of developing ATEs when compared with controls (OR 2.26, 95%CI: 1.38-3.68, p=0.001). Sensitivity analysis indicated that the significance estimate of pooled ORs was not significantly influenced by omitting any single study. In subgroup analyses, the odds ratio of ATEs did not significantly vary with tumor types (p=0.70), VEGFR-TKIs (p=0.32), treatment regimens (p=0.76), phase of trials (p=0.37) and sample size (p=0.89). Additionally, the most common events for ATEs were cardiac ischemia/infarction (67.4%), CNS ischemia (7.9%) and cerebrovascular accident (6.7%). CONCLUSION: In this largest meta-analysis to date, we find that treatment with VEGFR-TKIs significantly increase the risk of developing ATEs. Further studies are still needed to investigate this association. In the appropriate clinical scenario, the use of these drugs remains justified in their approved indications.