GametesOmics: A Comprehensive Multi-omics Database for Exploring the Gametogenesis in Humans and Mice.

Gametogenesis plays an important role in the reproduction and evolution of species. The transcriptomic and epigenetic alterations in this process can influence the reproductive capacity, fertilization, and embryonic development. The rapidly increasing single-cell studies have provided valuable multi-omics resources. However, data from different layers and sequencing platforms have not been uniformed and integrated, which greatly limits their use for exploring the molecular mechanisms that underlie oogenesis and spermatogenesis. Here, we develop GametesOmics, a comprehensive database that integrates the data of gene expression, DNA methylation, and chromatin accessibility during oogenesis and spermatogenesis in humans and mice. GametesOmics provides a user-friendly website and various tools, including Search and Advanced Search for querying the expression and epigenetic modification(s) of each gene; Tools with Differentially expressed gene (DEG) analysis for identifying DEGs, Correlation analysis for demonstrating the genetic and epigenetic changes, Visualization for displaying single-cell clusters and screening marker genes as well as master transcription factors (TFs), and MethylView for studying the genomic distribution of epigenetic modifications. GametesOmics also provides Genome Browser and Ortholog for tracking and comparing gene expression, DNA methylation, and chromatin accessibility between humans and mice. GametesOmics offers a comprehensive resource for biologists and clinicians to decipher the cell fate transition in germ cell development, and can be accessed at http://gametesomics.cn/.

2,3',4,4',5-Pentachlorobiphenyl induces mitochondria-dependent apoptosis mediated by AhR/Cyp1a1 in mouse germ cells.

Polychlorinated biphenyls (PCBs) are environmental organic pollutants widely used in industry that can bioaccumulate and affect the reproductive systems of male animals of different species. 2,3',4,4',5-Pentachlorobiphenyl (PCB118) is a representative of the 209 toxic PCB congeners. In this study, male mice were exposed to PCB118 at 0, 50, and 500 µg/kg/day for 35 days beginning 3-4 weeks after birth. The results of the study showed that PCB118 exposure during puberty reduced testicular quality, caused tissue damage, decreased sperm motility and sperm count, and increased malformation and testicular cell apoptosis in mice. Moreover, PCB118 increased the oxidative stress levels in sperm and testicular tissue and the expression of aryl hydrocarbon receptor (AhR) and Cyp1a1 and siginificantly decreased the level of nuclear factor-erythroid 2-related factor 2 (Nrf2). The results indicate that PCB118 can activate the AhR/Cyp1a1 pathway and inhibit Nrf2 expression to aggravate testicular oxidative stress and induce cell apoptosis, resulting in testicular and sperm quality damage.

Adsorption of sulfur on Au(111) surface: An extremely stable configuration.

The sulfur adsorption on gold surface is a hot topic in catalysis, electrochemistry and chemical sensors. However, the multiple structures of adsorbed sulfur and sulfur-induced reconstruction in gold substrate topography are still open problems until now. Here we performed an extensively study on sulfur adsorption on Au(111) surface based on First-Principles calculation. Our results show that the sulfur adsorption with additional Au atoms is not favorable. Thus, the well-known lifting of the herringbone reconstruction of Au(111) after sulfur adsorption can't be attributed to the lifting gold atoms. More importantly, we proposed an extremely stable configuration of S-Au(111) surface characterized by (√3 × âˆš3)R30° at 0.33 coverage, in which each S atom is chemisorbed in 3-fold coordinated sites and all the surface-Au atoms are terminated. Finally, the good agreement between our simulated STM and LEED images and experimental observations illuminates the truth that our proposed configuration is also favorable in experiment. This super stable S-adsorbed surface can be used as a starting point for the growth of two dimensional transition metal sulfides.

NIR-excited upconversion nanoparticles used for targeted inhibition of Aß42 monomers and disassembly of Aß42 fibrils.

Much attention has been paid to oxidising amyloid-ß peptides (Aß) for inhibiting their aggregation using photosensitive materials. However, the low penetration of ultraviolet/visible light into biological tissues and low targeting properties of the materials hinder their application. Here, we constructed a novel platform for attenuating the neurotoxicity of Aß through functional upconversion nanoparticles (UCNPs@SiO2-ThS). UCNPs@SiO2-ThS can not only inhibit the aggregation of Aß42 monomers, but also disassemble Aß42 fibrils by its selective photooxidative capacity under the irradiation of near-infrared (NIR) light. Moreover, based on the enhancement of ThS fluorescence after attaching to Aß42 fibrils, only Aß42 fibrils exposed to both UCNPs@SiO2-ThS and light can be oxidized rather than other normal proteins. To further enhance Aß-target photooxygenation, we introduced the Aß-target peptide (KLVFF) on the surface. Compared to traditional chemotherapies and radiotherapies, this novel PDT strategy shows remarkably reduced side effects and improved targeting.

Chain structure and ß conformation of poly(9,9-dioctylfluorene) (PFO) with different molecular weights delivering from the solution to the film in a drop-casting process.

Over the last decade, considerable attention has been paid to the formation mechanism of the ordered ß conformation for PFO both in the solution and film to prepare high-efficiency optoelectronic devices. However, the process of solvent evaporation and aggregates transferred from the solution to the film also play key roles in forming ordered structures, which have been neglected. In this study, the influence of molecular weight on the above process was systematically studied using techniques such as SLS/DLS, UV-Vis, PL, and TEM. Five samples with different Mw ranging from 25 100 Da to 117 000 Da were obtained by the precipitation fractionation method. In dilute THF solution, the molecular chains were in α conformation without aggregates. In films, as the molecular weight increased, the content of ß conformation and ordered structure increased first and then decreased. By studying the solvent evaporation process, for the first time, we propose a possible mechanism for the transformation process of chain structure and ß conformation from the solution to the film, which involves three stages. This study reveals the transformation process of the chain structure and ß conformation of PFO from the solution to the film and its relationship with the molecular weight, which provides theoretical and practical versions for in-depth understanding and control of the formation of the ordered structure in high-efficiency films.

Effect of Ligand Structures on Ligand-Protected Gold Clusters: [Au-(p-/m-/o-MBT)]1-8 Clusters.

The controllable preparation of ligand-protected clusters is still an unresolved problem, which may be due to that their formation mechanism is unclear. We propose that the ligand is the key to solve the above problems. Here, by using p-, m-, and o-methylbenzenethiol ligand protected gold clusters as examples, we try to explore the effect of ligand structures on ligand-protected gold clusters. The geometrical structures, relative stabilities and surface properties of small-sized ligand-protected gold clusters [Au-SR]1-8 (SR = p-/m-/o-MBT) have been systematically studied based on the density functional theory. The results show that the ground state structures of [Au-SR]1-8 clusters tend to form closed rings except for [Au-SR]1,2. The different structures of ligand have significant effect on the structures and stabilities of ligand-protected clusters. By analyzing their surface properties and possible growth patterns, it is found that [Au-SR]1,2 clusters serve as the basic building blocks, and the larger clusters can be regarded as the combinations of them. This study provides some insights into the effect of ligands on ligand-protected clusters, which is useful for understanding the formation mechanism of ligand-protected clusters.

Preimplantation genetic testing for structural rearrangement based on low-coverage next-generation sequencing accurately discriminates between normal and carrier embryos for patients with translocations.

RESEARCH QUESTION: Can preimplantation genetic testing for structural rearrangement (PGT-SR) based on low-coverage next-generation sequencing (NGS) accurately discriminate between normal and carrier embryos of reciprocal translocation (RecT) and Robertsonian translocation (RobT)? DESIGN: A total of 109 couples with RecT or RobT were included in this study. The ages, bad obsteric histories (BOH), blood karyotype and IVF cycle information, including the number of cumulus-oocyte complexes, metaphase II oocytes, two pronuclei oocytes and blastocysts were recorded. 0.1 × whole genome sequencing (WGS) of embryos followed by copy number variation (identifying unbalanced/balanced) and 2 × WGS of parents and embryos followed by haplotype analysis (discriminating between normal and carrier) were carried out in PGT-SR cycles. The embryos without translocation were transferred and clinical outcomes evaluated. RESULTS: Among all the couples in this study, 67 patients had RecT and 42 had RobT. After unbalanced and balanced detection, 103 balanced embryos underwent a further normal and carrier discrimination procedure, and 53 normal embryos were identified. Finally, 32 normal embryos were transferred, with an ongoing pregnancy rate of 46.88% (15/32). All ongoing pregnancies underwent amniocentesis, and the amninocentesis karyotyping results showed 100% concordance with PGT-SR diagnosis. CONCLUSIONS: Our low-coverage NGS-based PGT-SR method can accurately discriminate between normal and carrier status of balanced embryos. The method is cost-effective and has broad clinical applicability.

Single-cell RNA sequencing reveals abnormal fluctuations in human eight-cell embryos associated with blastocyst formation failure.

Infertility has become a global health issue, with the number of people suffering from the disease increasing year by year, and ART offering great promise for infertility treatment. However, the regulation of early embryonic development is complicated and a series of processes takes place, including the maternal-to-zygotic transition. In addition, developmental arrest is frequently observed during human early embryonic development. In this study, we performed single-cell RNA sequencing on a biopsied blastomere from human eight-cell embryos and tracked the developmental potential of the remaining cells. To compare the sequencing results between different eight-cell embryos, we have combined the research data of this project with the data previously shared in the database and found that cells from the same embryo showed a higher correlation. Additionally, the transcriptome of embryos with blastocyst formation failure was significantly different from developed embryos, and the gene expression as well as cell signaling pathways related to embryonic development were also altered. In particular, the expression of some maternal and zygotic genes in the failed blastocyst formation group was significantly altered: the overall expression level of maternal genes was significantly higher in the failed blastocyst than the developed blastocyst group. In general, these findings provide clues for the causes of human embryonic arrest after the eight-cell stage, and they also provide new ideas for improving the success rate of ART in clinical practice.

Intrauterine exposure to 2,3',4,4',5-pentachlorobiphenyl alters spermatogenesis and testicular DNA methylation levels in F1 male mice.

Polychlorinated biphenyls (PCBs) are synthetic biphenyl compounds with high toxicity. There are a total of 209 homologs, among which 2,3',4,4',5-pentachlorobiphenyl (PCB118) is one of the dioxin-like PCBs. PCB118 can accumulate in pregnant mice, leading to fetus directly exposure during development. The stage of migration of mouse primordial germ cells ranges from 8.5 to 13.5 days of pregnancy, which is the stage undergoing a genome-wide DNA demethylation process. In this study, the mice were exposed to 20 µg/kg/day and 100 µg/kg/day PCB118 from 8.5 to 13.5 days of pregnancy. During the embryo stage at 18.5 days (E18.5 days), the expression level of DNA methyltransferase 1 (Dnmt1) was reduced in the testes, and the DNA methylation level in mouse testes were also decreased. We found that the seminiferous tubules showed vacuolization and that the sperm deformity rate increased in the treated groups compared with the control group in 7-week-old mice. Because exposure to PCB118 during pregnancy causes damage to the reproductive system of male offspring mice, attention should be devoted to the toxicity transmission of persistent environmental pollutants such as PCBs.

DevOmics: an integrated multi-omics database of human and mouse early embryo.

Transcriptomic and epigenetic alterations during early embryo development have been proven to play essential roles in regulating the cell fate. Nowadays, advances in single-cell transcriptomics and epigenomics profiling techniques provide large volumes of data for understanding the molecular regulatory mechanisms in early embryos and facilitate the investigation of assisted reproductive technology as well as preimplantation genetic testing. However, the lack of integrated data collection and unified analytic procedures greatly limits their usage in scientific research and clinical application. Hence, it is necessary to establish a database integrating the regulatory information of human and mouse early embryos with unified analytic procedures. Here, we introduce DevOmics (http://devomics.cn/), which contains normalized gene expression, DNA methylation, histone modifications (H3K4me3, H3K9me3, H3K27me3, H3K27ac), chromatin accessibility and 3D chromatin architecture profiles of human and mouse early embryos spanning six developmental stages (zygote, 2cell, 4cell, 8cell, morula and blastocyst (ICM, TE)). The current version of DevOmics provides Search and Advanced Search for retrieving genes a researcher is interested in, Analysis Tools including the differentially expressed genes (DEGs) analysis for acquiring DEGs between different types of samples, allelic explorer for displaying allele-specific gene expression as well as epigenetic modifications and correlation analysis for showing the dynamic changes in different layers of data across developmental stages, as well as Genome Browser and Ortholog for visualization. DevOmics offers a user-friendly website for biologists and clinicians to decipher molecular regulatory mechanisms of human and mouse early embryos.

Effects of Polychlorinated Biphenyls on Animal Reproductive Systems and Epigenetic Modifications.

Polychlorinated biphenyls (PCBs) are a group of highly toxic endocrine-disrupting chemicals comprising 209 homologs. PCBs are extensively found in the environment and can induce typical estrogenic and profound, long-lasting effects on animals. In this article, the introduction of PCB residues into the environment and the pathways of PCB enrichment in animals are described. PCBs are widely deposited and eventually accumulate in human tissues and body fluids through biomagnification. PCBs can significantly decrease animal fertility and interfere with endocrine processes, leading to the development of various diseases and even cancer. The effects of PCBs on the reproductive systems of animals can also be passed to their offspring, indicating that PCBs may affect the epigenetic modification process. There is currently no treatment to effectively inhibit the toxicity of PCBs in organisms; therefore, the severity of PCB toxicity needs to be widely recognized.

Effects of 2,3',4,4',5-pentachlorobiphenyl exposure during pregnancy on DNA methylation in the testis of offspring in the mouse.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants, and the widespread use of PCBs has had adverse effects on human and animal health. This study experiment explored the effects of 2,3',4,4',5-pentachlorobiphenyl (PCB118) on the mammalian reproductive system. PCB118 was administered to pregnant mice from 7.5 to 12.5 days of gestation; F1 mice were obtained and the reproductive system of F1 male mice was examined. PCB118 damaged the reproductive system in male F1 mice, as evidenced by negative effects on the testicular organ coefficient (testes weight/bodyweight), a decrease in the diameter of seminiferous tubules and a significant reduction in the anogenital distance in 35-day-old F1 mice. In addition, methylation levels of genomic DNA were reduced, with reductions in the expression of the DNA methyltransferases DNMT1, DNMT3A and DNMT3B, as well as that of the epigenetic regulatory factor ubiquitin like with PHD and ring finger domains 1 (Uhrf1). Together, the results of this study provide compelling evidence that exposure of pregnant mice to PCB118 during primordial germ cell migration in the fetus affects the reproductive system of the offspring and decreases global methylation levels in the testis.

Effects of intrauterine exposure to 2,3',4,4',5-pentachlorobiphenyl on the reproductive system and sperm epigenetic imprinting of male offspring.

Polychlorinated biphenyls (PCBs) are a class of persistent organic environmental pollutants with a total of 209 homologs. The homolog 2,3',4,4',5-pentachlorobiphenyl (PCB118) is one of the most important dioxin-like PCBs and is highly toxic. PCB118 can accumulate in human tissues, serum and breast milk, which leads to direct exposure of the fetus during development. In the present study, pregnant mice were exposed to 0, 20 and 100 µg/kg/day of PCB118 during the stage of fetal primordial germ cell migration. Compared with the control group, we found morphological alterations of the seminiferous tubules and a higher sperm deformity rate in the male offspring in the treatment groups. Furthermore, the methylation patterns in the treatment groups of the imprinted genes H19 and Gtl2 in the sperm were altered in the male offspring. We also characterized the disturbance of the expression levels of DNA methyltransferase 1 (Dnmt1), Dnmt3a, Dnmt3b, Dnmt3l, and Uhrf1. The results indicated that intrauterine exposure to low doses of PCB118 could significantly damage the reproductive health of the male offspring. Therefore, attention should be paid to the adverse effects of PCB118 exposure during pregnancy on the reproductive system of male offspring.

Deletion of BAF250a affects oocyte epigenetic modifications and embryonic development.

BRG1-associated factor 250a (BAF250a) is a component of the SWI/SNF adenosine triphosphate-dependent chromatin remodeling complex, which has been shown to control chromatin structure and transcription. BAF250a was reported to be a key component of the gene regulatory machinery in embryonic stem cells controlling self-renewal, differentiation, and cell lineage decisions. Here we constructed Baf250aF/F ;Gdf9-cre (Baf250aCKO ) mice to specifically delete BAF250a in oocytes to investigate the role of maternal BAF250a in female germ cells and embryo development. Our results showed that BAF250a deletion did not affect folliculogenesis, ovulation, and fertilization, but it caused late embryonic death. RNA sequencing analysis showed that the expression of genes involved in cell proliferation and differentiation, tissue morphogenesis, histone modification, and nucleosome remodeling were perturbed in Baf250aCKO MII oocytes. We showed that covalent histone modifications such as H3K27me3 and H3K27ac were also significantly affected in oocytes, which may reduce oocyte quality and lead to birth defects. In addition, the DNA methylation level of Igf2r, Snrpn, and Peg3 differentially methylated regions was decreased in Baf250aCKO oocytes. Quantitative real-time polymerase chain reaction analysis showed that the relative messenger RNA (mRNA) expression levels of Igf2r and Snrpn were significantly increased. The mRNA expression level of Dnmt1, Dnmt3a, Dnmt3l, and Uhrf1 was decreased, and the protein expression in these genes was also reduced, which might be the cause for impaired imprinting establishment. In conclusion, our results demonstrate that BAF250a plays an important role in oocyte transcription regulation, epigenetic modifications, and embryo development.

Effects of 2,3',4,4'5-pentachlorobiphenyl exposure during pregnancy on epigenetic imprinting and maturation of offspring's oocytes in mice.

Polychlorinated biphenyls (PCBs) are a class of organic pollutants that have been widely found in the environment. The chemical 2,3',4,4'5-pentachlorobiphenyl (PCB118) is an important dioxin-like PCB compound with strong toxicity. PCB118 can accumulate in adipose tissue, serum and milk in mammals, and it is highly enriched in the follicular fluid. In this study, pregnant mice were exposed to 0, 20 and 100 µg/kg/day of PCB118 during pregnancy at the fetal primordial germ cell migration stage. The methylation patterns of the imprinted genes H19, Snrpn, Peg3 and Igf2r as well as the expression levels of Dnmt1, 3a, 3b and 3l, Uhrf1, Tet2 and Tet3 in fully grown germinal vesicle oocytes were measured in offspring. The rates of in vitro maturation, in vitro fertilization, oocyte spindle and chromosomal abnormalities were also calculated. The results showed that prenatal exposure to PCB118 altered the DNA methylation status of differentially methylated regions in some imprinted genes, and the expression levels of Dnmt1, 3a, and 3l, Uhrf1 and Tet3 were also changed. In addition, PCB118 disturbed the maturation process of progeny mouse oocytes in a dose-dependent manner. Therefore, attention should be paid to the potential impacts of PCB118-contaminated dietary intake during pregnancy on the offspring's reproductive health.

[Effect of conservative and conventional oxygen therapy on the prognosis of critically ill patients: a Meta-analysis].

OBJECTIVE: To compare the efficacy and safety of conservative and conventional oxygen therapy in critically ill patients. METHODS: Relevant literature and randomized controlled trials (RCTs) about the effect of conservative oxygen therapy and conventional oxygen therapy on the prognosis of intensive care unit (ICU) critically ill patients was searched from CNKI, VIP, Wanfang Data, Chinese Clinical Trial Registry, PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov by using the keywords "critically ill patients, conservative oxygen therapy, liberal oxygen therapy, conventional oxygen therapy, mortality" until October 30th in 2018. The main outcome indicators were short-term mortality (28-day mortality or ICU mortality); secondary indicators were 90-day mortality, duration of mechanical ventilation, the length of ICU stay, total hospitalization time, new infection rate in ICU and incidence of new organ dysfunction in ICU. In the conservative oxygen therapy group, the aim of pulse oxygen saturation (SpO2) was 0.90-0.92 or the arterial partial oxygen pressure (PaO2) was 70-100 mmHg (1 mmHg = 0.133 kPa), while in conventional oxygen therapy group SpO2 > 0.96 or PaO2 > 150 mmHg. Literature search, quality evaluation and data extraction was conducted independently by the two authors. The quality of these study was evaluated using Cochrane risk deviation assessment tool, and the relevant data were analyzed using RevMan 5.3 software. RESULTS: Four studies were included in the analysis, these studies were assessed as moderate to high quality studies. A total of 1 076 patients were enrolled, with 539 in the conservative oxygen therapy group and 537 in the conventional oxygen therapy group. Compared with conventional oxygen therapy group, short-term mortality [odds ratio (OR) = 0.66, 95% confidence interval (95%CI) = 0.50-0.87, P = 0.003] and the incidence of new organ dysfunction in ICU (OR = 0.64, 95%CI = 0.41-0.99, P = 0.04) were significantly decreased in conservative oxygen therapy group, duration of mechanical ventilation was significantly prolonged [standardized mean difference (SMD) = 17.17, 95%CI = 7.14-27.21, P = 0.000 8]. But there was no significantly difference in 90-day mortality (OR = 0.83, 95%CI = 0.59-1.17, P = 0.28), new infection rate in ICU (OR = 0.90, 95%CI = 0.66-1.21, P = 0.47), the length of ICU stay (SMD = -0.22, 95%CI = -1.02-0.59, P = 0.60) and total hospitalization time (SMD = 1.44, 95%CI = -1.43-4.31, P = 0.32) between the two groups. CONCLUSIONS: Compared with conventional oxygen therapy, conservative oxygen therapy can reduce short-term mortality and the incidence of organ dysfunction in critically ill patients, but cannot decrease the length of ICU stay and total hospitalization time.

[Comparison of the structures of the medical staff and the operation situations of the departments of critical care medicine between the provincial and county level hospitals of Guizhou Province in 2017].

OBJECTIVE: To understand the situations of departments of intensive care units (ICUs) of different level hospitals in Guizhou Province, and to provide directions and evidences for improving quality control in critical care medicine. METHODS: A county-level hospital and a provincial-level hospital's comprehensive ICU in Guizhou Province were selected to record and analyze and compare the structural indicators, patient admission and transfer, disease distribution, ventilator associated pneumonia (VAP), intravascular catheter related blood stream infection (CRBSI) and catheter-associated urinary tract infection (CAUTI) of the two hospitals' comprehensive ICU in 2017. RESULTS: The ICU of the People's Hospital of Suiyang County (county hospital) was found in 2012, and the ICU of the Affiliated Hospital of Guizhou Medical University (provincial hospital) was found in 1994. Until 2017, there were 10 and 46 beds, 6 (all of them hold bachelor's degree) and 18 physicians (6 of them hold PhD, 5 of them hold master's degree, 7 of them hold bachelor's degree), 17 (4 of them hold bachelor's degree, 13 of them hold college degree or graduated from secondary school) and 69 nurses (2 of them hold master's degree, 53 of them hold bachelor's degree, 14 of them hold college degree or graduated from secondary school) in the two ICUs respectively, there were significant differences in the education background of the physicians and nurses between the two ICUs (both P < 0.01). During 2017, 471 cases were admitted to the ICU of the county hospital while 1 633 cases were admitted to the ICU of the provincial hospital. Compared with the ICU of the provincial hospital, the ratio of the patients with acute physiology and chronic health evaluation II (APACHE II) ≥ 15 at admission was lower (74.8% vs. 85.1%, P < 0.01), the ratio of direct admission was higher (30.8% vs. 17.4%, P < 0.01), the ratio of the patients admitted to the ICU more than once was lower (0.8% vs. 5.0%, P < 0.01), the ratio of the patients whose the length of ICU stay less than 24 hours was higher (51.6% vs. 13.7%, P < 0.01), the ratio of the patients whose the length of ICU stay more than 28 days was lower (1.1% vs. 2.9%, P < 0.05), the ratio of the patients discharged against-advice (25.5% vs. 20.5%, P < 0.05) was higher, the ratio of the patients transferred to other hospitals was higher (5.1% vs. 0.3%, P < 0.05), and the ICU mortality was lower (4.0% vs. 13.9%, P < 0.01) in the ICU of the county hospital. The top three kinds of diseases treated in the ICU of the county hospital were brain injury (27.4%), trauma (19.1%) and toxication (6.8%); while in the ICU of the provincial hospital were brain injury (18.6%), sepsis (16.2%) and severe acute pancreatitis (4.8%). In addition, the incidences of VAP, CRBSI and CAUTI in the ICU of the county hospital were 10.0/1 000 ventilator days, 1.4/1 000 catheter days, 0.5/1 000 catheter days; while in the ICU of the provincial hospital were 5.8/1 000 ventilator days, 2.0/1 000 catheter days, 3.7/1 000 catheter days, respectively. CONCLUSIONS: There are short of physicians and nurses in the ICU of the provincial and county hospitals in Guizhou Province, and the educational level of the medical staff in the ICU of the county hospital is relatively low. Moreover, there were significant differences in the admissions and treatments and the outcomes of the critically ill patients between the two ICUs. The characteristics of the ICUs of county hospitals should be fully considered when the quality control of critical care medicine and continuing medical education are done.

Chinese medicine Tongxinluo capsule alleviates cerebral microcirculatory disturbances in ischemic stroke by modulating vascular endothelial function and inhibiting leukocyte-endothelial cell interactions in mice: A two-photon laser scanning microscopy study.

OBJECTIVE: The aim of this study was to examine the effect of TXL, a Chinese medicine prescription, on cerebral microcirculatory disturbances after pMCAO in mice using TPLSM and further explore the underlying mechanisms. METHODS: Adlut male C57BL/6J mice were subjected to pMCAO and orally administered with TXL (3.0, 1.5 and 0.75 g/kg/d) at 1, 3, and 21 hours after pMCAO. The following parameters were examined at 6 and 24 hours after pMCAO: neurological deficits, infarct volume, BBB permeability, cerebral microvessel structure, brain microcirculation (TPLSM imaging), vasoactive factors, and adhesion molecules. RESULTS: TXL improved neurological deficits, reduced infarct volume, attenuated BBB disruption, protected cerebral microvessel structure, increased cerebral capillary flow velocity and volume flux, and inhibited leukocyte-endothelial cell interactions at 6 or 24 hours after pMCAO. The therapeutic efficacy was exerted in a dose-dependent manner. Further study revealed that TXL (high dose) regulated the expression of PGI2, TXA2, and ET-1, and suppressed ICAM-1 and P-selectin. CONCLUSIONS: TXL alleviates cerebral microcirculatory disturbances against ischemic injury by modulating endothelial function and inhibiting leukocyte-endothelial cell interactions. These effects are associated with regulating the expression of PGI2, TXA2, and ET-1, and suppressing ICAM-1 and P-selectin expression.

[Effect of Jinlida on changes in expression of skeletal muscle lipid transport enzymes in fat-induced insulin resistance ApoE -/- mice].

OBJECTIVE: To study the effect of Jinlida on changes in expression of skeletal muscle lipid transport enzymes in fat-induced insulin resistance ApoE -/- mice. METHOD: Eight male C57BL/6J mice were selected in the normal group (NF), 40 male ApoE -/- mice were fed for 16 weeks, divided into the model group (HF), the rosiglitazone group ( LGLT), the Jinlida low-dose group (JLDL), the Jinlida medium-dose group (JLDM), the Jinlida high-dose group (JLDH) and then orally given drugs for 8 weeks. The organization free fatty acids, BCA protein concentration determination methods were used to determine the skeletal muscle FFA content. The Real-time fluorescent quantitative reverse transcription PCR ( RT-PCR) and Western blot method were adopted to determine mRNA and protein expressions of mice fatty acids transposition enzyme (FAT/CD36), carnitine palm acyltransferase 1 (CPT1), peroxide proliferators-activated receptor α( PPAR α). RESULT: Jinlida could decrease fasting blood glucose (FBG), cholesterol (TC), triglyceride (TG), free fatty acid (FFA) and fasting insulin (FIns) and raise insulin sensitive index (ISI) in mice to varying degrees. It could also up-regulate mRNA and protein expressions of CPT1 and PPARα, and down-regulate mRNA and protein levels of FAT/CD36. CONCLUSION: Jinlida can improve fat-induced insulin resistance ApoE -/- in mice by adjusting the changes in expression of skeletal muscle lipid transport enzymes.

Synthesis, biological evaluation, and molecular docking studies of N-((1,3-diphenyl-1H-pyrazol-4-yl)methyl)aniline derivatives as novel anticancer agents.

A series of N-((1,3-diphenyl-1H-pyrazol-4-yl)methyl)aniline derivatives (5a-8d) have been designed and synthesized, and their biological activities were also evaluated as potential antitumor and cyclin dependent kinase 2 (CDK2) inhibitors. Among all the compounds, compound 5a displayed the most potent CDK2/cyclin E inhibitory activity in vitro, with an IC(50) of 0.98 ± 0.06 µM. Antitumor assays indicated that compound 5a owned high antiproliferative activity against MCF-7 and B16-F10 cancer cell lines with IC(50) values of 1.88 ± 0.11 and 2.12 ± 0.15 µM, respectively. Docking simulation was performed to insert compound 5a into the crystal structure of CDK2 at active site to determine the probable binding model. Based on the preliminary results, compound 5a with potent inhibitory activity in tumor growth may be a potential anticancer agent.