Applying the OMOP Common Data Model to Facilitate Benefit-Risk Assessments of Medicinal Products Using Real-World Data from Singapore and South Korea / 대한의료정보학회지

Objectives@#The aim of this study was to characterize the benefits of converting Electronic Medical Records (EMRs) to a common data model (CDM) and to assess the potential of CDM-converted data to rapidly generate insights for benefit-risk assessments in post-market regulatory evaluation and decisions. @*Methods@#EMRs from January 2013 to December 2016 were mapped onto the Observational Medical Outcomes Partnership-CDM (OMOP-CDM) schema. Vocabulary mappings were applied to convert source data values into OMOP-CDM-endorsed terminologies. Existing analytic codes used in a prior OMOP-CDM drug utilization study were modified to conduct an illustrative analysis of oral anticoagulants used for atrial fibrillation in Singapore and South Korea, resembling a typical benefit-risk assessment. A novel visualization is proposed to represent the comparative effectiveness, safety and utilization of the drugs. @*Results@#Over 90% of records were mapped onto the OMOP-CDM. The CDM data structures and analytic code templates simplified the querying of data for the analysis. In total, 2,419 patients from Singapore and South Korea fulfilled the study criteria, the majority of whom were warfarin users. After 3 months of follow-up, differences in cumulative incidence of bleeding and thromboembolic events were observable via the proposed visualization, surfacing insights as to the agent of preference in a given clinical setting, which may meaningfully inform regulatory decision-making. @*Conclusions@#While the structure of the OMOP-CDM and its accessory tools facilitate real-world data analysis, extending them to fulfil regulatory analytic purposes in the post-market setting, such as benefit-risk assessments, may require layering on additional analytic tools and visualization techniques.

Recent advances in the application of nanobody technology: a review / 生物工程学报

As a malleable and novel tool for antigen recognition and modulation, nanobodies have the advantages of small size, easiness of expression, screening and modification, as well as high affinity and stability. Nanobodies are capable of recognizing more cryptic antigenic epitopes that are difficult to be recognized by traditional antibodies, making them increasingly used in the diagnosis and treatment of various diseases and assays. Nanobodies are also playing an irreplaceable role in the basic research. This review summarized the recent development of nanobodies and their derivatives in the detection of small molecules, pathogenic microorganisms and diagnosis of diseases, as well as in the fields of targeted therapies, cellular and molecular imaging. Broad prospects of nanobodies in the field of protein conformation studies were also reviewed.

Female adopted Chinese-American youth's sense of exclusion and short-and long-term adjustment.

In this article, we tested if female adopted Chinese youth's sense of exclusion predicted their behavioral adjustment and mental disorder diagnoses concurrently (Study 1) and longitudinally 5 years later (Study 2). In Study 1, 224 adoptees (M = 13.6 years, SD = 2.1) provided survey data on sense of exclusion (as indexed by ethnic marginality, ethnic identity search, and negative feelings toward adoption) and Internalizing Problems (i.e., anxiety, withdrawal, and somatic complaints), measured with the Child Behavior Checklist (CBCL)-Youth Self-Report. In Study 1, the adoptive parents additionally completed the CBCL parent-report on the adopted children's Internalizing Problems and reported if the adopted children had any mental disorder diagnoses. In Study 2, 60 youth from Study 1 (M = 18.6 years, SD = 2.1) completed the 3rd edition of the Behavioral Assessment System for Children-Self Report of Personality (BASC-3-SRP) that measures School Problems (i.e., negative attitudes toward teacher, negative attitudes toward school, and sensation seeking), Internalizing Problems (i.e., atypicality, locus of control, social stress, anxiety, depression, sense of inadequacy, and somatization), Attention-Deficit/Hyperactivity Disorder (ADHD; i.e., inattention and hyperactivity), and Personal Adjustment (i.e., relations with parents, peer relations, self-esteem, and self-reliance). They also responded to questions on receiving mental disorder diagnoses and treatments. We found that in Study 1, 33.2% of the youth had at least one diagnosis, with Anxiety Disorder (21.4%), ADD/ADHD (16.7%), and Attachment Disorder (7.5%) being the top three disorders. In Study 2, 40.3% had at least one diagnosis, with Anxiety Disorder (25.0%), Depression (21.7%), and ADD/ADHD (16.7%) being the top three disorders. Path analyses showed that in Study 1, ethnic marginality and negative feelings about adoption, but not ethnic identity search, significantly predicted parent-reported and self-reported Internalizing Problems; in Study 2, none of the three indicators of sense of exclusion predicted the adopted youth's adjustment. Implications for clinical practice and future research were discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Molecular mechanisms of mutualistic and antagonistic interactions in a plant-pollinator association.

Many insects metamorphose from antagonistic larvae into mutualistic adult pollinators, with reciprocal adaptation leading to specialized insect-plant associations. It remains unknown how such interactions are established at molecular level. Here we assemble high-quality genomes of a fig species, Ficus pumila var. pumila, and its specific pollinating wasp, Wiebesia pumilae. We combine multi-omics with validation experiments to reveal molecular mechanisms underlying this specialized interaction. In the plant, we identify the specific compound attracting pollinators and validate the function of several key genes regulating its biosynthesis. In the pollinator, we find a highly reduced number of odorant-binding protein genes and an odorant-binding protein mainly binding the attractant. During antagonistic interaction, we find similar chemical profiles and turnovers throughout the development of galled ovules and seeds, and a significant contraction of detoxification-related gene families in the pollinator. Our study identifies some key genes bridging coevolved mutualists, establishing expectations for more diffuse insect-pollinator systems.

Current opinions and developments of non-pharmacological treatments of hypertension based on sympathetic nervous system / 中国临床药理学与治疗学

Hypertension is a serious disease that endangers human health. Although the clinical efficiency of anti-hypertensive drugs have achieved good results, there are still many different types of resistant hypertension such as drug tolerance, and the incidence of complications of hypertension such as heart failure and stroke is still high. Therefore, the development and application of non-pharmacological treatment strategies have become an important aspect of the treatment of hypertension. The sympathetic nervous system plays a key role in the pathogenesis of hypertension. At present, most non-pharmacological treatment technologies for the prevention and treatment of hypertension mainly target the sympathetic nerve function. These technologies mainly include deep brain stimulation and renal denervation. Central iliac arteriovenous anastomosis, baroreflex activation therapy, endovascular baroreflex amplification, carotid body ablation, etc. This review focuses on the application status and related advantages and disadvantages of the above-mentioned non-pharmacological treatment methods based on the sympathetic nervous system, and provides new ideas and multiple options for treatment of hypertension.

Effects of combination of pargyline and doxorubicin on proliferation and migration of tripple negative breast cancer 4T-1 cells / 中国药理学通报

Aim To study the combination of lysinespecifc demethylase 1 (lysine-specifc demethylase 1, LSD1) inhibitor pargyline and the chemotherapy drug doxorubicin on the proliferation, migration and invasion of murine triple negative breast cancer 4T-1 cells. Methods In vitro, the effect on the proliferation, invasion and migration of 4T-1 cells of the combination of these two drugs were detected with CCK-8 method, lactate dehydrogenase release test, Chou-Talay method, Scratch test, Transwell assay, Western blot and etc. Tumor-bearing mice were used to investigate the combined effect of these two drugs on the proliferation of 4T-1 cells in vivo. Results The combination of pargyline and doxorubicin effectively inhibited the proliferation, migration and invasion of 4T-1 cells. Compared with single drug group, the combination of these two drugs could significantly inhibit the proliferation of breast cancer and prolong the survival time of mice with triple negative breast cancer. Conclusions The combined application of pargyline and doxorubicin has a synergistic inhibitory effect on the proliferation, migration and invasion of mouse breast cancer 4T-1 cells, and has potential value for clinical treatment on triplenegative breast cancer.

Behaviors of ADHD and Peer Relationship Difficulties in Chinese and American Youths: Role of Co-Occurring Behaviors of Depression and Anxiety.

The co-occurrence of behaviors of attention-deficit/hyperactivity disorder (ADHD) with behaviors of anxiety or behaviors of depression is the norm, but little is known on how the co-occurrence accounted for youths' peer relations. The authors report results on difficult peer relations in relation to behaviors of ADHD, co-occurring behaviors of depression, and behaviors of anxiety from three studies on 862 youths in China and in the United States. Study 1 included 313 ethnically and socioeconomically diverse American youths; Study 2 included 250 youths who were adopted out of Chinese orphanages by American parents; and Study 3 included 299 youths from Beijing, China. Data on difficult peer relations and behaviors of ADHD, depression, and anxiety were collected with the third edition of Behavior Assessment System for Children-Self Report of Personality. In all three studies, each type of problems alone significantly predicted difficult peer relations, but behaviors of ADHD were not significant when co-occurring behaviors of depression or co-occurring behaviors of anxiety were considered. Despite that the youths in our study had different cultural and personal backgrounds, there was no evidence that behaviors of ADHD were detrimental to youths' peer relations when behaviors of depression or anxiety were considered. Implications for intervention were discussed.

Effect of Capsaicin in Inhibiting Migration and Invasion of Breast Cancer MCF-7 Cells by Down-regulating SIRT1 / 中国实验方剂学杂志

Objective: To investigate the effect of capsaicin on the migration and invasion of human breast cancer MCF-7 cells and the underlying molecular mechanism. Method: Three capsaicin intervention groups of different concentrations (25, 50, 75 μmol·L-1) and a blank group were set up. After MCF-7 cells were treated with different concentrations of capsaicin (25, 50, 75 μmol·L-1) for 24 h, the cell migration and invasion abilities were assessed by Transwell migration and invasion assay, respectively. Meanwhile, the mRNA level of silent information regulator 2 homolog 1 (SIRT1) and DNA polymerase δ catalytic subunit p125 encoding gene POLD1 (POLD1) were detected by Real-time polymerase chain reaction (Real-time PCR). The protein levels of SIRT1 and DNA polymerase δ catalytic subunit p125 (p125) were detected by Western blot. Result: Compared with the blank group, the number of transmembrane cells was significantly reduced, and the mobility was significantly decreased (P-1) in MCF-7 cells for 24 h. Capsaicin (25, 50, 75 μmol·L-1) significantly down-regulated the mRNA and protein expressions of SIRT1 (P-1) in MCF-7 cells for 24 h. Furthermore, capsaicin (25, 50, 75 μmol·L-1) also significantly down-regulated the mRNA expression of POLD1 and the protein expression of p125 (P-1) in MCF-7 cells for 24 h. Conclusion: Capsaicin remarkably inhibits the cell migration and invasion of breast cancer MCF-7 cells, and the possible mechanism may be related to the down-regulation of SIRT1 and POLD1 mRNA expression levels and SIRT1 and p125 protein expression levels.

Inhibitory Effect of Capsaicin on Growth of Breast Cancer MDA-MB-231 Cells Transplanted Tumor in Nude Mice / 中国实验方剂学杂志

Objective: To investigate the inhibitory effect of capsaicin on the growth of breast cancer MDA-MB-231 cells transplanted tumour in nude mice and its possible molecular mechanism. Method: Transplanted tumor model of breast cancer MDA-MB-231 cells in nude mice were established. Then the tumor-bearing mice were randomly divided into 4 groups:model group, and low, medium and high-dose capsaicin groups (5, 10, 20 mg·kg-1). Mice of low, medium and high-dose capsaicin groups (5, 10, 20 mg·kg-1) were intraperitoneally injected with the corresponding dose of capsaicin, and the model group was injected with the same volume of phosphate buffer saline (PBS), once every 3 days, for a total of 8 times in succession. Body weight of mice and transplantation tumor volume were measured before each injection of capsaicin. Mice of each group were put to death 24 h after the last administration, and then the tumor volume, mass and the tumor inhibitory rate were calculated. The protein expression levels of high mobility group box 1 (HMGB1) and Toll-like receptors 4(TLR4) were measured by immunohistochemistry and Western blot. Result: No significant difference was observed between each group in body weight. However, compared with the model group, capsaicin (5, 10, 20 mg·kg-1) remarkably inhibited the tumor volume and mass (PPP-1) also markedly inhibited the protein expression levels of HMGB1 and TLR4 (PConclusion: Capsaicin remarkably inhibits the growth of breast cancer MDA-MB-231 cells transplanted tumour in nude mice, and the possible mechanism may be related to the down-regulation of HMGB1 and TLR4 at the protein level.

Angiotensin-Converting Enzyme 2 in the Rostral Ventrolateral Medulla Regulates Cholinergic Signaling and Cardiovascular and Sympathetic Responses in Hypertensive Rats / 神经科学通报·英文版

The rostral ventrolateral medulla (RVLM) is a key region in cardiovascular regulation. It has been demonstrated that cholinergic synaptic transmission in the RVLM is enhanced in hypertensive rats. Angiotensin-converting enzyme 2 (ACE2) in the brain plays beneficial roles in cardiovascular function in hypertension. The purpose of this study was to determine the effect of ACE2 overexpression in the RVLM on cholinergic synaptic transmission in spontaneously hypertensive rats (SHRs). Four weeks after injecting lentiviral particles containing enhanced green fluorescent protein and ACE2 bilaterally into the RVLM, the blood pressure and heart rate were notably decreased. ACE2 overexpression significantly reduced the concentration of acetylcholine in microdialysis fluid from the RVLM and blunted the decrease in blood pressure evoked by bilateral injection of atropine into the RVLM in SHRs. In conclusion, we suggest that ACE2 overexpression in the RVLM attenuates the enhanced cholinergic synaptic transmission in SHRs.

Effects of FBI-1 silencing on proliferation and apoptosis of triple-negative breast cancer cell line MDA-MB-231 / 生理学报

This work aimed to observe the effects of short hairpin RNA (shRNA)-silenced FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) on proliferation and apoptosis of triple-negative breast cancer cell line MDA-MB-231. qRT-PCR and Western blot analysis were applied to detect the mRNA and/or protein expression of FBI-1, Bcl-2, Bax, cleaved-Caspase 3 and Survivin. RNA interference method was used to silence FBI-1 expression in MDA-MB-231 cells. CCK-8 and colony formation assay were employed to detect the cell proliferation. Flow cytometry was employed for examining cell apoptosis. In vivo tumorigenicity of MDA-MB-231 cells was detected by tumor transplantation in nude mice. The results showed that the mRNA and protein expressions of FBI-1 were higher in MDA-MB-231 cells compared with those in normal human mammary epithelial cells MCF-10A. FBI-1 gene silencing inhibited proliferation and induced apoptosis of MDA-MB-231 cells in vitro, together with decreased Bcl-2 and Survivin protein expression, increased Bax protein expression and activated Caspase 3. Moreover, FBI-1 gene silencing inhibited the tumorigenesis of MDA-MB-231 cells in vivo. These results suggest that silencing of FBI-1 gene inhibits proliferation, induces apoptosis and suppresses the tumorigenesis of MDA-MB-231 cells.

Effect of electroacupuncture at Neiguan (PC 6) and Baihui (GV 20) on CHOP and caspase-12 gene expressions in rats after ischemia-reperfusion injury / 针灸推拿医学（英文版）

Objective:To investigate the effects of electroacupuncture (EA) at Neiguan (PC 6) and Baihui (GV 20) by observing the changes of CCAAT/enhancer-binding protein(C/EBP) homologous protein (CHOP) and caspase-12 gene expressions in rats after cerebral ischemia-reperfusion injury (IRI), and explore whether the apoptosis pathway of endoplasmic reticulum stress (ERS) is involved in the protective mechanisms of EA. Methods:Sixty rats were randomly assigned to five groups (12 in each group): a normal control group (group A), a sham-operation group (group B), an operation group (group C), an Edaravone group (group D) and an EA group (group E). The cerebral IRI rat model was induced by middle cerebral artery occlusion (MCAO) using intraluminal monofilament. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was adopted in the measurement of cerebral infarction volume. Real-time polymerase chain reaction (RT-PCR) was used to determine the mRNA expressions of CHOP and caspase-12. Results: Compared with group A and group B, the volume of cerebral infarction and mRNA expressions of CHOP and caspase-12 in group C, group D and group E were increased, with statistical significances (P0.05). Conclusion:EA at Neiguan (PC 6) and Baihui (GV 20) can effectively suppress the volume of cerebral infarction. Furthermore, the underlying mechanism of EA at Neiguan (PC 6) and Baihui (GV 20) is possibly related to the down-regulation of CHOP and caspase-12 mRNA expressions, so as to decrease cell apoptosis.

Size and Composition Effects in Sb-Carbon Nanocomposites for Sodium-Ion Batteries.

Sodium-ion batteries are in the spotlight as viable alternatives to lithium-ion batteries in stationary storage and power grid applications. Among possible anode materials, Sb is one of the interesting candidates due to a combination of battery-type potential plateaus in the charge-discharge profiles, high capacity (theoretical capacity of 660 mAh g-1), and demonstrated good cyclic stability. The influence of Sb particle size (particularly at the nanoscale range) and the composition of Sb-carbon composites on the electrode performance, stability, and charge storage mechanism is systematically evaluated here for the first time. A range of Sb-carbon nanocomposites with varied Sb particle size (between 50 and ∼1 nm) are studied. The control of the particle size is achieved via varying the carbon and Sb weight ratio in the precursors. The shape of charge-discharge profiles, hysteresis, and the difference in cyclic stabilities and rate performance are analyzed. The nanocomposite with the smallest particle size (∼1 nm) and the largest carbon content provides the most stable cyclic behavior and a better rate capability but suffers from an increased hysteresis between charge and discharge curves. In situ synchrotron X-ray diffraction experiments indicate that the storage mechanism in the Sb-carbon nanocomposites containing Sb nanoparticles is different from the electrodes with bulkier, micron-sized Sb particles, and the electrochemical reaction proceeds through a number of crystalline intermediates.

Gas Protection of Two-Dimensional Nanomaterials from High-Energy Impacts.

Two-dimensional (2D) materials can be produced using ball milling with the help of liquid surfactants or solid exfoliation agents, as ball milling of bulk precursor materials usually produces nanosized particles because of high-energy impacts. Post-milling treatment is thus needed to purify the nanosheets. We show here that nanosheets of graphene, BN, and MoS2 can be produced by ball milling of their bulk crystals in the presence of ammonia or a hydrocarbon ethylene gas and the obtained nanosheets remain flat and maintain their single-crystalline structure with low defects density even after a long period of time; post-milling treatment is not needed. This study does not just demonstrate production of nanosheets using ball milling, but reveals surprising indestructible behaviour of 2D nanomaterials in ammonia or hydrocarbon gas under the high-energy impacts; in other milling atmospheres such as air, nitrogen or argon the same milling treatment produces nanosized particles. A systematic study reveals chemisorption of ammonia and hydrocarbon gases and chemical reactions occurring at defect sites, which heal the defects by saturating the dangling bonds. Density functional theory was used to understand the mechanism of mechanochemical reactions. Ball milling in ammonia or hydrocarbon is promising for mass-production of pure nanosheets.

Analysis of perception control and influencing factors in patients with lung cancer undergoing chemotherapy / 中国实用护理杂志

Objective To analyze the perceived control of lung cancer patients undergoing chemotherapy and to explore its influencing factors. Methods A total of 185 patients with lung cancer were recruited and assessed by homemade general information questionnaire and the Cancer Experience and Efficacy Scale. Results The total score of cancer experience during chemotherapy in patients with lung cancer was (62.50±6.99) points. The total score of efficacy during chemotherapy in patients with lung cancer was (42.52±8.08) points. Single factor analysis showed the influencing factors of perceived control were personal income, sex, education, metastasis, surgical treatment and stage of disease. Conclusions The cancer-related experience and efficacy of patients with lung cancer is at middle level. Health-care worker should pay attention to the impact of lung cancer patients and take effective measures to mitigate the negative cancer-related experience, thereby improving the perceived control of the lung cancer patients.

Research progress the evaluation method of medication and exercise compliance of patients with stroke / 中国实用护理杂志

Based on the review of literature, the evaluation method and application of medication and functional exercise compliance of patients with stroke were summarized, to provide reference for nursing staff about the effective evaluation of medication and exercise compliance of patients with stroke, as well as the early and accurate judgment of patient′s compliance, further taking nursing intervention measures, to provide a basis for improving the medication and functional exercise compliance of patients with stroke and their rehabilitation effect.

Lithium storage in disordered graphitic materials: a semi-quantitative study of the relationship between structure disordering and capacity.

The application of the graphitic anode is restricted by its low theoretical specific capacity of 372 mA h g(-1). Higher capacity can be achieved in the graphitic anode by modifying its structure, but the detailed storage mechanism is still not clear. In this work, the mechanism of the lithium storage in a disordered graphitic structure has been systematically studied. It is found that the enhanced capacity of the distorted graphitic structure does not come from lithium-intercalation, but through a capacitive process, which depends on the disordering degree and the porous structure.

Dielectric screening in atomically thin boron nitride nanosheets.

Two-dimensional (2D) hexagonal boron nitride (BN) nanosheets are excellent dielectric substrate for graphene, molybdenum disulfide, and many other 2D nanomaterial-based electronic and photonic devices. To optimize the performance of these 2D devices, it is essential to understand the dielectric screening properties of BN nanosheets as a function of the thickness. Here, electric force microscopy along with theoretical calculations based on both state-of-the-art first-principles calculations with van der Waals interactions under consideration, and nonlinear Thomas-Fermi theory models are used to investigate the dielectric screening in high-quality BN nanosheets of different thicknesses. It is found that atomically thin BN nanosheets are less effective in electric field screening, but the screening capability of BN shows a relatively weak dependence on the layer thickness.

MicroRNAs in microglia polarization and CNS diseases: mechanism and functions / 生理学报

Microglia are resident macrophages of central nervous system (CNS), and thus act as the crucial stuff of immune response and play very important roles in the progress of various CNS diseases. There are two different polarization statuses of activated microglia, M1 and M2 phenotypes. M1 polarized microglia are important for eradicating bacterial and promoting inflammation, whereas M2 cells are characterized by anti-inflammation and tissue remodeling. Recently, more and more evidence indicated that different polarized microglia showed diverse microRNA (miRNA) expression profiles. MiRNAs regulate microglia polarization, and thus affect the progress of CNS diseases. Fully exploring the polarization status of microglia during CNS diseases and the role of miRNAs in microglia polarization will be very helpful for a deep understanding of the roles of microglia in immunopathologic mechanism of different CNS diseases and offer the theoretical foundation of searching more effective therapies for these disorders.

Observation of active sites for oxygen reduction reaction on nitrogen-doped multilayer graphene.

Active sites and the catalytic mechanism of nitrogen-doped graphene in an oxygen reduction reaction (ORR) have been extensively studied but are still inconclusive, partly due to the lack of an experimental method that can detect the active sites. It is proposed in this report that the active sites on nitrogen-doped graphene can be determined via the examination of its chemical composition change before and after ORR. Synchrotron-based X-ray photoelectron spectroscopy analyses of three nitrogen-doped multilayer graphene samples reveal that oxygen reduction intermediate OH(ads), which should chemically attach to the active sites, remains on the carbon atoms neighboring pyridinic nitrogen after ORR. In addition, a high amount of the OH(ads) attachment after ORR corresponds to a high catalytic efficiency and vice versa. These pinpoint that the carbon atoms close to pyridinic nitrogen are the main active sites among the different nitrogen doping configurations.