Parent-adolescent discrepancies in positive parenting and adolescent problem behaviors in Chinese families.

Based on the discrepancy-maladaptive hypothesis and general strain theory, in this study, we examined two key aspects: first, the mediating role of self-control in the relationship between parent-adolescent discrepancies in positive parenting and adolescent internalizing and externalizing problems, and second, variations in problem behavior among subgroups with different parent-adolescent dyads reporting patterns. The participants were 349 intact Chinese families, with parents as the primary caregivers and teenagers aged 15-18 years who are attending secondary vocational schools. The results revealed that adolescents generally perceived lower levels of caring and behavioral control than parents. Compared to behavioral control, discrepancies in perceived levels of caring had more significant predicting levels of internalizing and externalizing problems, and the relationship between discrepancies of caring and internalizing and externalizing problems was mediated by self-control. Latent profile analysis revealed three parent-adolescent responding patterns (subgroups); compared to the other subgroups, only the subgroup characterized by adolescents perceiving lower caring and behavioral control than parents exhibited higher levels of internalizing and externalizing problems. The findings of this study provide insights on how parent-adolescent discrepancies may lead to adolescent problem behaviors and highlight the importance of self-control as a mediating mechanism.

Emotion and prospective memory: effects of emotional targets and contexts.

Event-based prospective memory (PM) refers to the ability to remember to perform a delayed and intended action when an event is encountered in the future. Whether emotional targets promote PM performance is still controversial. The reason for these inconsistent findings may be related to the degree of target arousal and context valence (the valence of ongoing task trials) in the previous studies. This study aimed to investigate the separate and combined effects of target valence, arousal, and context valence on event-based PM through two experiments. The results showed that the participants were faster and more accurate in responding to positive, negative, and high-arousal PM targets. Interestingly, an interaction effect of target valence, arousal, and context valence was observed, implying that their individual effects on PM performance cannot be understood in isolation. These findings demonstrate that positive, negative, and high-arousal PM targets can enhance PM performance. In addition, the results provided support for both the emotion enhancement account and the emotion-saliency account, depending upon whether the valence of the PM target matched or did not match the valence of the context. Moreover, context valence can modulate the effect of arousal on PM across different target valences.

[Influence of E-cadherin methylation on prognosis in children with acute lymphoblastic leukemia]. / å„¿ç«¥æ€¥æ€§æ·‹å·´ç»†èƒžç™½è¡€ç— ä¸­E-钙黏蛋白甲基化对预后的影响.

OBJECTIVES: To study the significance of E-cadherin and the association between E-cadherin methylation status and prognosis in children with acute lymphoblastic leukemia (ALL) by examining the mRNA and protein expression of E-cadherin and its gene methylation status in bone marrow mononuclear cells of children with ALL. METHODS: The samples of 5 mL bone marrow blood were collected from 42 children with ALL who were diagnosed for the first time at diagnosis (pre-treatment group) and on day 33 of induction chemotherapy (post-treatment group). RT-qPCR, Western blot, and methylation-specific PCR were used to measure the mRNA and protein expression of E-cadherin and the methylation level of the E-cadherin gene. The changes in each index after induction chemotherapy were compared. RESULTS: The mRNA and protein expression levels of E-cadherin in the post-treatment group were significantly higher than those in the pre-treatment group (P<0.05), while the positive rate of E-cadherin gene methylation in the post-treatment group was significantly lower than that in the pre-treatment group (P<0.05). At the end of the test, the children with negative methylation had significantly higher overall survival rate and event-free survival rate than those with positive methylation (P<0.05). CONCLUSIONS: E-cadherin expression is associated with the development of ALL in children, and its decreased expression and increased methylation level may indicate a poor prognosis.

Research progress of intelligent reversible drug delivery system / 药学学报

In the research on cancer theranostics, most environment-sensitive drug delivery systems can only achieve unidirectional and irreversible responsive changes under pathological conditions, thereby improving the targeting effect and drug release performance of the delivery system. However, such irreversible changes pose potential safety hazards when the dynamically distributed delivery system returns to the blood circulation or transports to the normal physiological environment. Intelligent reversible drug delivery systems can respond to normal physiological and pathological microenvironments to achieve bidirectional and reversible structural changes. This feature will help to precisely control the drug release of the delivery system, prolong the blood circulation time, improve the targeting efficiency, and avoid the potential safety hazards of the irreversible drug delivery system. In this review, we describe the research progress of intelligent reversible drug delivery system from two main aspects: controlled drug release and prolonged blood circulation time/enhanced cellular internalization of drug.

What Is Different about Teratoma-Associated Anti-LGI1 Encephalitis? A Long-Term Clinical and Neuroimaging Case Series.

INTRODUCTION: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is clinically heterogeneous, especially at presentation, and though it is sometimes found in association with tumor, this is by no means the rule. METHODS: Clinical data for 10 patients with anti-LGI1 encephalitis were collected including one case with teratoma and nine cases without and compared for clinical characteristics. Microscopic pathological examination and immunohistochemical assay of the LGI1 antibody were performed on teratoma tissue obtained by laparoscopic oophorocystectomy. RESULTS: In our teratoma-associated anti-LGI1 encephalitis case, teratoma pathology was characterized by mostly thyroid tissue and immunohistochemical assay confirmed positive nuclear staining of LGI1 in some tumor cells. The anti-LGl1 patient with teratoma was similar to the non-teratoma cases in many ways: age at onset (average 47.3 in non-teratoma cases); percent presenting with rapidly progressive dementia (67% of non-teratoma cases) and psychiatric symptoms (33%); hyponatremia (78%); normal cerebrospinal fluid results except for positive LGI1 antibody (78%); bilateral hippocampal hyperintensity on magnetic resonance imaging (44%); diffuse slow waves on electroencephalography (33%); good response to immunotherapy (67%); and mild residual cognitive deficit (22%). Her chronic anxiety and presentation with status epilepticus were the biggest differences compared with the non-teratoma cases. CONCLUSION: In our series, anti-LGI1 encephalitis included common clinical features in our series: rapidly progressive dementia, faciobrachial dystonic seizures, behavioral disorders, hyponatremia, hippocampal hyperintensity on magnetic resonance imaging, and residual cognitive deficit. We observed some differences (chronic anxiety and status epilepticus) in our case with teratoma, but a larger accumulation of cases is needed to improve our knowledge base.

Differential Peripheral Blood Glycoprotein Profiles in Symptomatic and Asymptomatic COVID-19

Glycosylation is the most common form of post-translational modification of proteins, critically affecting their structure and function. Using liquid chromatography and mass spectrometry for high-resolution site-specific quantification of glycopeptides coupled with high-throughput artificial intelligence-powered data processing, we analyzed differential protein glyco-isoform distributions of 597 abundant serum glycopeptides and non-glycosylated peptides in 50 individuals who had been seriously ill with COVID-19 and in 22 individuals who had recovered after an asymptomatic course of COVID-19. As additional comparison reference phenotypes, we included 12 individuals with a history of infection with a common cold coronavirus, 16 patients with bacterial sepsis, and 15 healthy subjects without history of coronavirus exposure. We found statistically significant differences, at FDR<0.05, for normalized abundances of 374 of the 597 peptides and glycopeptides interrogated, between symptomatic and asymptomatic COVID-19 patients. Similar statistically significant differences were seen when comparing symptomatic COVID-19 patients to healthy controls (350 differentially abundant peptides and glycopeptides) and common cold coronavirus seropositive subjects (353 differentially abundant peptides and glycopeptides). Among healthy controls and sepsis patients, 326 peptides and glycopeptides were found to be differentially abundant, of which 277 overlapped with biomarkers that showed differential expression between symptomatic COVID-19 cases and healthy controls. Among symptomatic COVID-19 cases and sepsis patients, 101 glycopeptide and peptide biomarkers were found to be statistically significantly abundant. Using both supervised and unsupervised machine learning techniques, we found specific glycoprotein profiles to be strongly predictive of symptomatic COVID-19 infection. LASSO-regularized multivariable logistic regression and K-means clustering yielded accuracies of 100% in an independent test set and of 96% overall, respectively. Our findings are consistent with the interpretation that a majority of glycoprotein modifications observed which are shared among symptomatic COVID-19 and sepsis patients likely represent a generic consequence of a severe systemic immune and inflammatory state. However, there are glyco-isoform changes that are specific and particular to severe COVID-19 infection. These may be representative of either COVID-19-specific consequences or of susceptibility to or predisposition for a severe course of the disease. Our findings support the potential value of glycoproteomic biomarkers in the biomedical understanding, and, potentially, the clinical management of serious acute infectious conditions.

Interleukin-13 promotes cellular senescence through inducing mitochondrial dysfunction in IgG4-related sialadenitis / 国际口腔科学杂志·英文版

Immunoglobulin G4-related sialadenitis (IgG4-RS) is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood. The aim of this study was to explore the role and mechanism of interleukin-13 (IL-13) in the cellular senescence during the progress of IgG4-RS. We found that the expression of IL-13 and IL-13 receptor α1 (IL-13Rα1) as well as the number of senescent cells were significantly higher in the submandibular glands (SMGs) of IgG4-RS patients. IL-13 directly induced senescence as shown by the elevated activity of senescence-associated β-galactosidase (SA-β-gal), the decreased cell proliferation, and the upregulation of senescence markers (p53 and p16) and senescence-associated secretory phenotype (SASP) factors (IL-1β and IL-6) in SMG-C6 cells. Mechanistically, IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6 (p-STAT6) and mitochondrial-reactive oxygen species (mtROS), while decreased the mitochondrial membrane potential, ATP level, and the expression and activity of superoxide dismutase 2 (SOD2). Notably, the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger MitoTEMPO. Moreover, IL-13 increased the interaction between p-STAT6 and cAMP-response element binding protein (CREB)-binding protein (CBP) and decreased the transcriptional activity of CREB on SOD2. Taken together, our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6-CREB-SOD2-dependent pathway in IgG4-RS.

Effect of Encoding on Prospective Memory.

Event-based prospective memory (ProM) refers to remembering to execute planned actions in response to a target ProM cues. Encoding modality influences ProM performance; visual encoding has been studied more than auditory encoding. Further, it has not yet been examined whether different encoding may influence ProM performance in different encoding modalities. This study examines the effects of encoding modality (visual vs. auditory), cue-encoding specificity (specific cue vs. non-specific cue), and encoding modes (standard vs. implementation intention) on event-based ProM tasks. In Experiment 1, cue specificity and encoding modality were manipulated as a within-groups encoding of visual cues is more commonly and between-groups variable. Results revealed the facilitative effect of cue specificity on ProM performance. Also, with respect to encoding modality, participants showed better performance when receiving auditory instructions compared with the visual encoding condition. In Experiment 2, as in Experiment 1, cue specificity and encoding modality were manipulated. Encoding mode was added as a new between-group variable. Result revealed that there was a significant interaction between encoding modality and encoding modes. Visual implementation intention encoding was a more effective method for improving ProM performance compared with visual standard encoding. Furthermore, there was a significant interaction between cue-encoding specificity and encoding modes. Implementation intention encoding enhances ProM performance in non-specific cue-encoding conditions. Overall, the present study found that (1) auditory encoding modality showed superior ProM performance compared with visual encoding, although implementation intention had facilitative on ProM performance regardless of the encoding modalities, and (2) there was better ProM performance under specific encoding compared with non-specific encoding, and implementation intention had a facilitative effect on ProM performance in the non-specific condition.

Phytosterols in hull-less pumpkin seed oil, rich in ∆7-phytosterols, ameliorate benign prostatic hyperplasia by lowing 5α-reductase and regulating balance between cell proliferation and apoptosis in rats.

BACKGROUND: Pumpkin seed oil is widely used to treat benign prostatic hyperplasia (BPH), a common disease in elder men. However, its active components and mechanism have remained to be elucidated. OBJECTIVE: The objective of the present study was to investigate the active components of pumpkin seed oil and its mechanism against BPH. DESIGN: Total phytosterol (TPS) was isolated from hull-less pumpkin (Cucurbita pepo L. var. Styriaca) seed oil and analyzed by gas chromatography/mass spectrometry (GC/MS). Three phytosterols were purified by preparative HPLC (high performance liquid chromatography) and confirmed by NMR (nuclear magnetic resonance). TPS (3.3 mg/kg body weight, 1 mL/day/rat) was administered intragastrically to the testosterone propionate-induced BPH rats for 4 weeks. The structure changes of prostate tissues were assessed by hematoxylin & eosin (H&E) staining. The expression of androgen receptor (AR) and steroid receptor coactivator 1 (SRC-1) was analyzed by immunohistochemistry, while that of 5α-reductase (5AR), apoptosis, or proliferation-related growth factors/proteins was detected by real-time quantitative polymerase chain reaction or western blotting. RESULTS: The ∆7-phytosterols in TPS reached up to 87.64%. Among them, 24ß-ethylcholesta-7,22,25-trienol, 24ß-ethylcholesta-7,25(27)-dien-3-ol, and ∆7-avenasterol were confirmed by NMR. TPS treatment significantly ameliorated the pathological prostate enlargement and restored histopathological alterations of prostate in BPH rats. It effectively suppressed the expressions of 5AR, AR, and coactivator SRC-1. TPS inhibited the expression of proliferation-related growth factor epidermal growth factor, whereas it increased the expressions of apoptosis-related growth factor/gene transforming growth factor-ß1. The proliferation-inhibiting effect was achieved by decreasing the ERK (extracellular signal-regulated kinase) phosphorylation, while apoptosis was induced by Caspase 3 activation through JNK (c-Jun N-terminal kinase) and p38 phosphorylation. CONCLUSION: TPS from hull-less pumpkin seed oil, with ∆7-phytosterols as its main ingredients, is a potential nutraceutical for BPH prevention.

Correlation analysis between advanced glycation end products detected noninvasively and skin aging factors.

OBJECTIVE: To investigate the correlation between advanced glycation end products (AGEs) and skin elasticity or blood perfusion values in healthy people of different age groups and to evaluate the relationship between noninvasive detection of AGEs and age or skin aging. METHODS: One hundred and two healthy people were enrolled and grouped into groups of 20 years old. Group I: 19-40 years old; Group II: 41-60 years old; Group III: 61-80 years old. Noninvasive techniques such as fluorescence spectroscopy and laser speckle flowmetry were used to detect AGEs levels, local skin perfusion value, and skin elasticity in skin tissue at all age groups. RESULT: The AGEs in the skin increased with age, and the difference between the three age groups was statistically significant (P < .05).There was no significant difference in gender between AGEs (P > .05).There was no significant relationship between AGEs and skin elasticity or blood perfusion value in the Group I; there was a low correlation between AGEs and skin elasticity in the 41-60 years age group (r < .4, P < .05). The level of AGEs in the elderly over 60 years was significantly positively correlated with skin elasticity and blooding perfusion value (r > .4, P < .05). CONCLUSION: There is a significant correlation between AGEs and age or skin aging indicators. As the age increasing, the level of AGEs increases obviously, which can be used as a potential noninvasive tool for detecting skin aging.

Evaluating Quantitative Measures of Microbial Contamination from China's Spacecraft Materials.

Different methods are used for the quantification of microbial load on spacecrafts. Here, we investigated a number of methodologies currently in use with the intent to identify the most accurate methods for the quantification of microbes on low-biomass metal surfaces such as those used in China's Space Station. In a previous study, we observed a high abundance of Bacillus sp. TJ 1-1 on interior surfaces of China's Space Station, and we therefore undertook this study in which we used a range of 102 to 109 cells/100 cm2 of this strain for setting different contamination levels. Four of the most common analytical approaches (contact plate, spread plate, quantitative PCR, and BacLight™) were used to quantify the number of viable microbial cells associated with the materials of China's Space Station. Results show that, for 102 cells/100 cm2, the contact plate method is the most convenient and reliable. For microbial contamination levels ≥103 cells/100 cm2 and a sampling area of 121 cm2, the BacLight method proved to be most reliable for the detection of live cells. Moreover, a sampling area of 121 cm2 was found to be the most suitable for analysis of metal surfaces for space station interiors, which are usually low in biomass. These results establish suitable sampling and processing methodologies for microbial enumeration of metal surfaces on China's Space Station.

Quantitative proteomics analysis of young and elderly skin with DIA mass spectrometry reveals new skin aging-related proteins.

Skin aging is a specific manifestation of the physiological aging process that occurs in virtually all organisms. In this study, we used data independent acquisition mass spectrometry to perform a comparative analysis of protein expression in volar forearm skin samples from of 20 healthy young and elderly Chinese individuals. Our quantitative proteomic analysis identified a total of 95 differentially expressed proteins (DEPs) in aged skin compared to young skin. Enrichment analyses of these DEPs (57 upregulated and 38 downregulated proteins) based on the GO, KEGG, and KOG databases revealed functional clusters associated with immunity and inflammation, oxidative stress, biosynthesis and metabolism, proteases, cell proliferation, cell differentiation, and apoptosis. We also found that GAPDH, which was downregulated in aged skin samples, was the top hub gene in a protein-protein interaction network analysis. Some of the DEPs identified herein had been previously correlated with aging of the skin and other organs, while others may represent novel age-related entities. Our non-invasive proteomics analysis of human epidermal proteins may guide future research on skin aging to help develop treatments for age-related skin conditions and rejuvenation.

Challenges in the Practice of Sexual Medicine in the Time of COVID-19 in China.

BACKGROUND: In March 2020, the World Health Organization declared coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Currently, data on changes in sexual behavior during the COVID-19 outbreak are limited. AIM: The present study aimed to obtain a preliminary understanding of the changes in people's sexual behavior, as a result of the pandemic, and explore the context in which they manifest. METHODS: A convenience sample of 270 men and 189 women who completed an online survey consisting of 12 items plus an additional question were included in the study. OUTCOMES: The study outcomes were obtained using a study-specific questionnaire to assess the changes in people's sexual behavior. RESULTS: While there was a wide range of individual responses, our results showed that 44% of participants reported a decrease in the number of sexual partners and about 37% of participants reported a decrease in sexual frequency. Multiple regression analysis showed that age, partner relationship, and sexual desire were closely related to sexual frequency. In addition, we found that most individuals with risky sexual experiences had a rapid reduction in risky sexual behavior. CLINICAL IMPLICATIONS: The current findings contribute to identifying another potential health implication associated with the COVID-19 pandemic and report preliminary evidence of the need to provide potential interventions for the population. STRENGTH & LIMITATIONS: This study is the first to perform a preliminary exploration of sexual behavior during the COVID-19 outbreak. The generalizability of the results is limited, given that only a small convenience sample was used. CONCLUSION: During the height of the COVID-19 outbreak, overall sexual activity, frequency, and risky behaviors declined significantly among young men and women in China. Li W, Li G, Xin C, et al. Challenges in the Practice of Sexual Medicine in the Time of COVID-19 in China. J Sex Med 2020;17:1225-1228.

Non­invasive proteome­wide quantification of skin barrier­related proteins using label­free LC­MS/MS analysis.

A number of epidermal proteins are closely related to skin barrier function, the abnormalities of which can lead to specific skin diseases. These proteins must be quantified to further investigate the changes in the skin barrier between healthy and disease states. However, the non­invasive and proteome­wide quantification of skin proteins without any labelling steps remains a challenge. In this study, 3M medical adhesive tapes were used to obtain skin samples from volunteers. Proteins were extracted from fresh skin samples and digested with trypsin. Each tryptic peptide was analysed in three replicates using liquid chromatography with tandem mass spectrometry analysis and label­free quantification. The data were searched against the Human Universal Protein Resource (UniProt) to match with known proteins. Using this method, 1,157 skin proteins recorded in the UniProt were quantified. A total of 50 identical proteins were identified in the three replicate analyses of all samples with no significant differences in abundance. The results provided an objective metric for further study of skin ageing and various skin diseases. Specifically, the non­invasive proteome­wide method used in this study can be applied to future studies of skin diseases related to barrier destruction by monitoring the changes in the levels of epidermal proteins.

Detection and Analysis of Ceramide in Skin and Blood in a Healthy Chinese Population.

To explore the significance of ceramide in the skin barrier and its potential utility within the cosmetics industry, an accurate and high-speed method was used to detect the types of ceramides in the skin and blood of a healthy Chinese population. Forearm cortical skin stratum corneum samples were obtained from four healthy subjects using a noninvasive method. In addition, these subjects were collected intravenously to obtain blood samples. Ceramides were detected in skin and blood samples using high-performance liquid chromatography coupled with specialized high-resolution Fourier Transform mass spectrometry machine. Data were analyzed using full-flow lipid analysis software. Peaks representing ceramides were detected in all skin samples and some blood samples. The results show that ceramides in skin are predominantly long-chain ceramides, but mainly short-chain in the blood. Simple and fast qualitative and quantitative analysis of ceramide in the skin and blood provides a basis for the precise addition of ceramide in future skin care products and the metabolic regulation and prevention of various diseases.

A novel mutation of COL7A1 in a Chinese DEB-Pt family and review of the literature.

BACKGROUND: Pretibial dystrophic epidermolysis bullosa (DEB-Pt) is an extremely rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by blistering and scar formation. The pathogenesis of the disease is mainly due to the mutation of COL7A1 gene encoding type VII collagen fibers, resulting in the destruction of the anchoring structure of the epidermis and dermis. AIMS: The purpose of this study was to discover the major mutations in DEB-Pt by studying this family and reviewing the literature on DEB-Pt. PATIENTS/METHODS: We examined the patients by clinical manifestations and histopathology, extracted DNA from blood samples from 7 individuals in the family via FlexiGene DNA Kit, and then sequenced the samples using whole-exon sequencing (WES). RESULT: Characteristic clinical manifestations such as blisters and scars were found in the patients. Genetic analysis revealed a missense mutation in exon 87(c.6860G>A) of COL7A1 gene, which has never been reported before. CONCLUSION: The discovery of the new mutation extends the COL7A1 mutation database. We also reviewed all the mutation in DEB-Pt from relevant literature at home and abroad. This will facilitate the molecular diagnosis, treatment, and prognosis of DEB-Pt.

Application and enlightenment of formative assessment in the innovation and development of higher education in basic medical science / 生理学报

Formative assessment aims at cultivating and improving students' comprehensive qualities and abilities. It acquires and analyzes the dynamic changes of students' learning process through flexible and diverse assessment methods. The assessment contents cover multiple aspects including knowledge, abilities, attitudes, literacy, etc., which help teachers and students to formulate practical and efficient improvement strategies and to meet the inherent needs of students for comprehensive development. This review describes the connotation of formative assessment and summarizes its application in higher education of basic medical science in China. The existing shortcomings and the reasonable advice are proposed. We also introduce our experience in the application of formative assessment in pathophysiology education. This review will provide reference and enlightenment for the reform and innovation of the assessment system in higher education of basic medical science.

Formulation Optimization of Citalopram Hydrobromide Thermosensitive Nasal Gel and Its In Vitro Properties / 中国药学杂志

OBJECTIVE: To optimize the formulation of citalopram hydrobromide (CTH ) thermosensitive nasal gel and further evaluate its in vitro properties. METHODS: With gelling temperature and gelling time as evaluating indexes, central composite design-response surface and single factor experimental design method were used to optimize the formulation of CTH thermosensitive nasal gel by using poloxamer 407(F127) and carbomer 940 (CP940) as gel materials. Meanwhile, nasal mucosa permeation enhancer for CTH was then sieved by using Franz diffusion cell and ex vivo sheep nasal mucosa as experimental model. Finally, CTH thermosensitive nasal gel was prepared with cold method and then its in vitro properties was evaluated. In vitro cumulative erosion and cumulative release rate of the drug thermosensitive nasal gel were investigated by membrane-free dissolution method and dialysis membrane method, respectively. Moreover, the effect of temperature and pH on the viscosity of the drug nasal gel formulation was also evaluated. RESULTS: The optimal formulation of the thermosensitive nasal gel consisted of CTH 8.0%, F127 20.27%, CP940 0.17%, DM-β-CD 3.0%, ethylparaben 0.05% and distilled water. The gelling temperature, gelling time and pH of the drug thermosensitive nasal gel were found to be about 32.5 ℃,42 s and 5.0, respectively. The in vitro cumulative erosion and cumulative release percentage were both greater than 90% in 55 min and furthermore there was good linear correlation between these two parameters (r=0.998 6). Additionally, in vitro cumulative release of the drug from the gel formulation was determined to be 92% within 8 h, which conformed to Higuchi kinetic equation. Furthermore, the viscosity of the drug nasal gel was influenced by temperature as well as pH in different extent. CONCLUSION: The optimized formulation of the CTH thermosensitive nasal gel with central composite design-response surface method and single factor design method shows suitable gelling temperature, gelling time, pH value for nasal preparation and obvious in vitro drug sustained release characteristics.

Pharmacokinetics and Brain Delivery of Citalopram Hydrobromide Thermosensitive Nasal Gel in Rats / 中国药学杂志

OBJECTIVE: To investigate the pharmacokinetics of citalopram hydrobromide(CTH)thermosensitive nasal gel and further evaluate its brain delivery in rats. METHODS: The concentrations of CTH in rat plasma and brain tissue were determined by HPLC method. With intragastric administration (ig) of CTH solution as control, CTH thermosensitive nasal gel was intranasally given to rats and the concentrations of CTH in plasma and brain tissues were then determined. Moreover, the main pharmacokinetic parameters of CTH in plasma and brain tissues such as tmax, ρmax,relative bioavailability (Fr) and drug targeting efficiency (DTE) were estimated. RESULTS: Main pharmacokinetic parameters of CTH following nasal and ig administration to rats such as tmax and ρmax were 5 and 45 min, 2 152.86 and 589.68 ng•mL-1 in plasma, and 5 and 45 min, 17 660.56 and 1 171.68 ng•g-1 in brain tissue, respectively. Finally, the Fr and DTE of CTH thermosensitive nasal gel were found to be 184.91% and 250.03%, respectively. CONCLUSION: CTH thermosensitive nasal gel may be an ideal non-oral new dosage form with many advantages such as rapid in vivo absorption, high bioavailability and obvious brain delivery characteristics.

ICGRM: integrative construction of genomic relationship matrix combining multiple genomic regions for big dataset.

BACKGROUND: Genomic prediction is an advanced method for estimating genetic values, which has been widely accepted for genetic evaluation in animal and disease-risk prediction in human. It estimates genetic values with genome-wide distributed SNPs instead of pedigree. The key step of it is to construct genomic relationship matrix (GRM) via genome-wide SNPs; however, usually the calculation of GRM needs huge computer memory especially when the SNP number and sample size are big, so that sometimes it will become computationally prohibitive even for super computer clusters. We herein developed an integrative algorithm to compute GRM. To avoid calculating GRM for the whole genome, ICGRM freely divides the genome-wide SNPs into several segments and computes the summary statistics related to GRM for each segment that requires quite few computer RAM; then it integrates these summary statistics to produce GRM for whole genome. RESULTS: It showed that the computer memory of ICGRM was reduced by 15 times (from 218Gb to 14Gb) after the genome SNPs were split into 5 to 200 parts in terms of the number of SNPs in our simulation dataset, making it computationally feasible for almost all kinds of computer servers. ICGRM is implemented in C/C++ and freely available via https://github.com/mingfang618/CLGRM. CONCLUSIONS: ICGRM is computationally efficient software to build GRM and can be used for big dataset.